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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

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