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Home / Equine Research Bank / Equine Vet J / Morphine synovial fluid concentrations after intravenous reg...
Equine veterinary journal2024; doi: 10.1111/evj.14114

Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation.

Abstract: Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. Objective: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Methods: Randomised cross-over in vivo experiment. Methods: Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay. Results: Measurable concentrations of morphine were apparent in the RCJ of all horses. Median C of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median C of synovial amikacin was 322.6 (157.5-1371.6 μg/mL). Conclusions: Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included. Conclusions: IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects. Unassigned: Die Zugabe von Morphin zum Perfusat bei der Durchführung der intravenösen regionalen Extremitätenperfusion (IVRLP) kann hilfreich sein, um schmerzhafte infektiöse orthopädische Zustände der distalen Extremität zu behandeln. Unassigned: Das Hauptziel dieser Studie war es, die synovialen Morphin‐Konzentrationen nach IVRLP mit Morphin allein oder in Kombination mit Amikacin zu bestimmen. Methods: Randomisierte Crossover‐Studie. Sechs Pferde erhielten eine IVRLP mit 0.1 mg/kg Morphinsulfat, verdünnt auf 60 mL mit 0.9% NaCl (M‐Gruppe) oder kombiniert mit 2 g Amikacin und 0.9% NaCl (MA‐Gruppe), mit einer zweiwöchigen Auswaschperiode zwischen den Behandlungen. Synovialflüssigkeit wurde aus dem Radiokarpalgelenk (RCJ) zu den Zeitpunkten 10, 20, 30, 120, 240, 480, 720 und 1440 Minuten nach IVRLP gesammelt. Der Tourniquet wurde nach der 30 minütigen Behandlung entfernt. Die synovialen Konzentrationen von Morphin und dessen Hauptmetaboliten wurden mittels Flüssigkeitschromatographie‐Tandem‐Massenspektrometrie gemessen. Die Amikacin‐Konzentrationen wurden durch ein Fluoreszenzpolarisations‐Immunoassay quantifiziert. Results: Messbare Konzentrationen von Morphin waren im RCJ aller Pferde nachzuweisen. Die mediane CMAX von Morphin in der M‐Gruppe betrug 4753.1 (2115.7–14 934.5) ng/mL und 4477 (3434.3–7363) ng/mL in der MA‐Gruppe (p = 0.5). Die mediane CMAX von synovialem Amikacin betrug 322.6 (157.5–1371.6 μg/mL). WICHTIGSTE EINSCHRÄNKUNGEN: Die Einschränkungen dieser Studie umfassen eine kleine Stichprobengröße. Die Untersuchenden waren über die Behandlungen nicht verblindet, und eine dritte Behandlungsgruppe, in der Amikacin allein über IVRLP an die Studienpopulation verabreicht wurde, war nicht eingeschlossen. Unassigned: IVRLP unter Verwendung von Morphin ist eine durchführbare Technik, und synoviale Morphin‐Konzentrationen waren nach IVRLP messbar und wurden nicht beeinflusst, wenn sie gleichzeitig mit Amikacin verwendet wurden. Die Verabreichung von Morphin über IVRLP könnte als analgetische Technik für orthopädische Zustände der distalen Extremität vorteilhaft sein, während potenziell ernsthafte systemische Nebenwirkungen begrenzt werden.
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Publication Date: 2024-06-17 PubMed ID: 38887833DOI: 10.1111/evj.14114Google Scholar: Lookup
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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 aimed at examining the use and effects of morphine in treating painful orthopedic conditions in horses when infused alongside amikacin via intravenous regional limb perfusion (IVRLP). The study determined the concentration levels of morphine present in the synovial fluid after IVRLP, with results indicating this method may be effective in managing pain while limiting potential systemic side-effects.

Research Objective and Methodology

  • The principal objective of this study was to determine the synovial fluid concentrations of morphine following IVRLP, performed either with morphine alone or in combination with the antibiotic drug amikacin.
  • The experiment was a randomised cross-over in vivo on six horses which underwent IVRLP with morphine, either alone or combined with amikacin.
  • The morphine dosage was 0.1 mg/kg, mixed to 60 mL with saline, either alone (M group) or combined with 2 g amikacin (MA group). The two treatments were separated by a two-week washout period.
  • Synovial fluid was collected for study purposes at a defined series of times ranging from 10 minutes to 24 hours after the IVRLP procedure.
  • A tourniquet, used for the blood flow restriction needed in IVRLP, was removed after 30 minutes.
  • The study intended to measure the synovial concentrations of morphine and its major metabolites using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified using a fluorescence polarisation immunoassay.

Research Findings and Limitations

  • Measurable levels of morphine were identified in the synovial fluid of all horses tested, irrespective of whether the morphine was administered alone or with amikacin. There was no statistical difference in morphine levels between the two groups.
  • This shows that the co-administration of amikacin did not materially affect the absorption of morphine into the synovial fluid.
  • The study’s limitations included a small sample size and the fact that the investigators were not blinded to the treatments being compared. Additionally, the study design did not include a control group where only amikacin was administered via IVRLP.

Research Conclusions

  • The research concludes that IVRLP using morphine is a feasible technique for the target animals. Synovial morphine concentrations were measurable and remained unaffected when used along with amikacin.
  • This study suggests that the administration of morphine via IVRLP can be a useful method of pain relief for distal limb orthopedic conditions in horses, and this approach may limit potential systemic side-effects compared to systemic morphine administration.

Cite This Article

APA
Kilcoyne I, Nieto J, Nottle BF, Flynn H, Knych HK. (2024). Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation. Equine Vet J. https://doi.org/10.1111/evj.14114

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Kilcoyne, Isabelle
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Nieto, Jorge
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Nottle, Bridget F
  • Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, USA.
Flynn, Harriet
  • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Grant Funding

  • CEH #21-V / UC Davis Center for Equine Health

References

This article includes 44 references
  1. Crabtree NE, Mochal‐King CA, Sloan PB, Eddy AL, Wills RW. Synovial butorphanol concentrations and mechanical nociceptive thresholds after intravenous regional limb perfusion in standing sedated horses.. Vet Surg 2019;48:1473–1482.
  2. Hunter BG, Parker JE, Wehrman R, Stang B, Cebra CK. Morphine synovial fluid concentrations after intravenous regional limb perfusion in standing horses.. Vet Surg 2015;44:679–686.
  3. Chabot‐Dore AJ, Schuster DJ, Stone LS, Wilcox GL. Analgesic synergy between opioid and alpha2‐adrenoceptors.. Br J Pharmacol 2015;172:388–402.
  4. Bennett RC, Steffey EP. Use of opioids for pain and anesthetic management in horses.. Vet Clin North Am Equine Pract 2002;18:47–60.
  5. Guedes A. Pain management in horses.. Vet Clin North Am Equine Pract 2017;33:181–211.
  6. Kalpravidh M, Lumb WV, Wright M, Heath RB. Effects of butorphanol, flunixin, levorphanol, morphine, and xylazine in ponies.. Am J Vet Res 1984;45:217–223.
  7. Figueiredo JP, Muir WW, Sams R. Cardiorespiratory, gastrointestinal, and analgesic effects of morphine sulfate in conscious healthy horses.. Am J Vet Res 2012;73:799–808.
  8. Roberts MC, Argenzio A. Effects of amitraz, several opiate derivatives and anticholinergic agents on intestinal transit in ponies.. Equine Vet J 1986;18:256–260.
  9. Lindegaard C, Frost AB, Thomsen MH, Larsen C, Hansen SH, Andersen PH. Pharmacokinetics of intra‐articular morphine in horses with lipopolysaccharide‐induced synovitis.. Vet Anaesth Analg 2010;37:186–195.
  10. 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;37:171–185.
  11. Santos LC, deMoraes AN, Saito ME. Effects of intraarticular ropivacaine and morphine on lipopolysaccharide‐induced synovitis in horses.. Vet Anaesth Analg 2009;36:280–286.
  12. vanLoon JP, Menke ES, L'Ami J, Jonckheer‐Sheehy VS, Back W, vanWeeren PR. Analgesic and anti‐hyperalgesic effects of epidural morphine in an equine LPS‐induced acute synovitis model.. Vet J 2012;193:464–470.
  13. Oreff GL, Dahan R, Tatz AJ, Raz T, Britzi M, Kelmer G. The effect of perfusate volume on amikacin concentration in the metacarpophalangeal joint following cephalic regional limb perfusion in standing horses.. Vet Surg 2016;45(5):625–630.
  14. Bergstrom TC, Kilcoyne I, Magdesian KG, Nieto JE. Increasing tourniquet number has no effect on amikacin concentration within the radiocarpal joint in horses undergoing intravenous regional limb perfusion.. Am J Vet Res 2022;83(4):364–370.
  15. Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Sutton GA. Time to peak concentration of amikacin in the antebrachiocarpal joint following cephalic intravenous regional limb perfusion in standing horses.. Vet Comp Orthop Traumatol 2020;33:327–332.
  16. Kilcoyne I, Nieto JE, Knych HK, Dechant JE. Time required to achieve maximum concentration of amikacin in synovial fluid of the distal interphalangeal joint after intravenous regional limb perfusion in horses.. Am J Vet Res 2018;79:282–286.
  17. Kilcoyne I, Nieto J, Magdesian KG, Nottle BF. Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.. Vet Surg 2023;52(8):1171–1179.
  18. Moyer W, Schumacher J, Schumacher J. A guide to equine joint injection and regional anesthesia.. Yardley, PA: Veterinary Learning Systems; 2007. p. 92–95.
  19. Sole A, Nieto JE, Aristizabal FA, Snyder JR. Effect of emptying the vasculature before performing regional limb perfusion with amikacin in horses.. Equine Vet J 2016;48:737–740.
  20. Knych HK, Steffey EP, McKemie DS. Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses.. J Vet Pharmacol Ther 2014;37:374–381.
  21. Clinical and Laboratory Standards Institute Subcommittee on Antimicrobial Susceptibility Testing. In: Proceedings of the 2019 Meeting Clinical and Laboratory Standards Institute.. Clinical and Laboratory Standards Institute Clinical and Laboratory Standards Institute. Available from: www.CLSI.org. Accessed May 2023.
  22. Lacy MK, Nicolau DP, Nightingale CH, Quintiliani R. The pharmacodynamics of aminoglycosides.. Clin Infec Dis 1998;27:23–27.
  23. Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration.. J Infect Dis 1987;155:93–99.
  24. Murphey ED, Santschi EM, Papich MG. Regional intravenous perfusion of the distal limb of horses with amikacin sulfate.. J Vet Pharmacol Ther 1999;22:68–71.
  25. Kelmer G, Bell GC, Martin‐Jimenez T, Saxton C, Catasus S, Elliot B. Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses.. J Vet Pharmacol Ther 2013;36(3):236–240.
  26. Kelmer G, Martin‐Jimenez T, Saxton AM, Catasus C, Elliot SB, Laktriz J. Evaluation of regional limb perfusion with erythromycin using the saphenous, cephalic, or palmar digital veins in standing horses.. J Vet Pharmacol Ther 2013;36:434–440.
  27. Kelmer G, Tatz AJ, Famini S, Bdolah‐Abram T, Soback S, Britzi M. Evaluation of regional limb perfusion with chloramphenicol using the saphenous or cephalic vein in standing horses.. J Vet Pharmacol Ther 2015;38:35–40.
  28. Kelmer G, Tatz AJ, Kdoshim E, Britzi M, Segev G. Evaluation of the pharmacokinetics of imipenem following regional limb perfusion using the saphenous and the cephalic veins in standing horses.. Res Vet Sci 2017;114:64–68.
  29. Kilcoyne I, Nieto JE, Galuppo LD, Dechant JE. Time required to achieve maximum amikacin concentration in the synovial fluid of the tarsocrural joint following administration of the drug by intravenous regional limb perfusion in horses.. Am J Vet Res 2021;82:99–104.
  30. Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.. Can J Vet Res 2016;80:230–235.
  31. Oreff GL, Tatz AJ, Dahan R, Segev G, Haberman S, Britzi M. Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses.. Vet Surg 2017;46:1120–1125.
  32. Parra‐Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S. Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses.. Am J Vet Res 2006;67:1687–1695.
  33. Rubio‐Martinez LM, Lopez‐Sanroman J, Cruz AM, Santos M, Andres MS, Roman FS. Evaluation of safety and pharmacokinetics of vancomycin after intravenous regional limb perfusion in horses.. Am J Vet Res 2005;66:2107–2113.
  34. 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;45:798–803.
  35. Andersen G, Christrup L, Sjogren P. Relationships among morphine metabolism, pain and side effects during long‐term treatment: an update.. J Pain Symptom Manage 2003;25:74–91.
  36. Gupta A, Bodin L, Holmstrom B, Berggren L. A systematic review of the peripheral analgesic effects of intraarticular morphine.. Anesth Analg 2001;93:761–770.
  37. Kalso E, Tramer MR, Carroll D, McQuay HJ, Moore RA. Pain relief from intra‐articular morphine after knee surgery: a qualitative systematic review.. Pain 1997;71:127–134.
  38. Bergstrom J, Ahmed M, Li J, Ahmad T, Kreicbergs A, Spetea M. Opioid peptides and receptors in joint tissues: study in the rat.. J Orthop Res 2006;24:1193–1199.
  39. Sheehy JG, Hellyer PW, Sammonds GE, Mama KR, Powers BE, Hendrickson DA. Evaluation of opioid receptors in synovial membranes of horses.. Am J Vet Res 2001;62:1408–1412.
  40. Ashley FH, Waterman‐Pearson AE, Whay HR. Behavioural assessment of pain in horses and donkeys: application to clinical practice and future studies.. Equine Vet J 2005;37:565–575.
  41. Love EJ, Murrell J, Whay HR. Thermal and mechanical nociceptive threshold testing in horses: a review.. Vet Anaesth Analg 2011;38:3–14.
  42. Beccar‐Varela AM, Epstein KL, White CL. Effect of experimentally induced synovitis on amikacin concentrations after intravenous regional limb perfusion.. Vet Surg 2011;40:891–897.
  43. vanLoon JP, deGraw JC, Brunott A, Weerts EA, vanWeeren PR. Upregulation of articular synovial membrane u‐opioid‐like receptors in an acture synovitis model.. Vet J 2013;196:1408–1412.
  44. Stein C. Intra‐articular morphine for inflammatory pain.. Reg Anesth Pain Med 2006;31:496–497.

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