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

BACKGROUND: 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. OBJECTIVES: The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. STUDY DESIGN: 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 CMAX 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 CMAX of synovial amikacin was 322.6 (157.5-1371.6 µg/mL). MAIN LIMITATIONS: 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.

Effect of Procaine Penicillin G and Flunixin Meglumine on Serum Amyloid A Response in Healthy Adult Horses.

This study was designed to determine the effect of PPG and/or flunixin meglumine on SAA response when used at clinical dosing regimens in healthy adult horses. Six healthy adult horses were enrolled in a crossover study design including one control and three treatment groups: no treatment (control); PPG alone (intramuscularly q12h for 72h); flunixin meglumine alone (intravenously q24h for 72h); and PPG (intramuscularly q12h for 72h) and flunixin meglumine (intravenously q24h for 72h). Whole blood was collected at 0, 24, 48, 72, 96 and 120 hours post-initial drug administration to measure SAA using a commercial lateral-flow immunoassay. The washout period was 30 days. Individual SAA values were within the reference range (≤ 20 µg/mL) for almost all horses in the control group. One control horse displayed a SAA value of 28 µg/mL at 72 hours. All horses from the PPG group showed normal SAA values throughout the study. Apart from one horse (SAA of 24 µg/mL at 96 hours) from the flunixin meglumine group, all horses showed normal SAA values. For the PPG and flunixin meglumine group, 5 horses had SAA values within reference range. One horse displayed increased SAA values (32-45 µg/mL) between 48 to 96 hours post-drug administration. There was no difference in area under the SAA time curve amongst control and treatment groups (P > 0.05). The administration of intramuscular PPG and/or intravenous flunixin meglumine does not trigger an inflammatory response that induces a SAA value above reference range in most adult healthy horses.

Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.

OBJECTIVE: To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (CMAX ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. STUDY DESIGN: Randomized crossover study. ANIMALS: Seven healthy adult horses. METHODS: The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. Amikacin concentrations were quantified by a fluorescence polarization immunoassay. The mean CMAX and time to peak concentration (TMAX ) of amikacin within the RCJ were determined. A one-sided paired t-test was used to determine the differences between treatments. The significance level was p < .05. RESULTS: The mean ± SD CMAX in the DMSO group was 1361.8 ± 593 µg/mL and in the 0.9% NaCl group it was 860 ± 481.6 µg/mL (p = .058). Mean TMAX using the 10% DMSO solution was 23 and 18 min using the 0.9% NaCl perfusate (p = .161). No adverse effects were associated with use of the 10% DMSO solution. CONCLUSION: Although there were higher mean peak synovial concentrations using the 10% DMSO solution no difference in synovial amikacin CMAX between perfusate type was detected (p = .058). CLINICAL SIGNIFICANCE: Use of a 10% DMSO solution in conjunction with amikacin during IVRLP is a feasible technique and does not negatively affect the synovial amikacin levels achieved. Further research is warranted to determine other effects of using DMSO during IVRLP.

Fibro-Osseous Lesions Of The Craniofacial Complex In Horses: 30 Cases (2001-2019).

OBJECTIVE: To describe the presentation, diagnosis, treatment, and outcome for horses with fibro-osseous lesions of the craniofacial complex. STUDY DESIGN: Retrospective multicenter case series. ANIMALS: Thirty horses evaluated for fibro-osseous lesions of the skull from January 1, 2001 through December 31, 2019 in four centers. METHODS: Medical records were reviewed for signalment, clinical presentation, histological and diagnostic imaging findings, treatment instituted, and outcome. Long-term outcome information was obtained by owner questionnaire or the medical record. RESULTS: Diagnoses included ossifying fibroma in 20 of 30 horses, osteoma in eight of 30 horses, and fibrous dysplasia in two of 30 horses. Twelve of 30 lesions were diagnosed in horses <1 year old, and 20 of 30 lesions originated from the rostral mandible. The most common treatment was rostral mandibulectomy. Recurrence was not reported after complete excision. Incomplete excision was confirmed in eight horses (four ossifying fibromas, three osteomas, and one fibrous dysplasia), and follow-up information was available for seven horses. Recurrence occurred in one horse, while six horses had long-term resolution of clinical signs. Prognosis for survival and return to use was excellent in 23 horses with long-term follow-up. CONCLUSION: Fibro-osseous lesions were uncommon in this multicenter study; they were most commonly diagnosed in young animals and most frequently affected the rostral mandible. Long-term survival was excellent. CLINICAL SIGNIFICANCE: The definitive diagnosis of fibro-osseous lesions of the craniofacial complex in horses is made from results of histopathology and cannot be determined on the basis of clinical presentation alone. Surgical excision is indicated, and prognosis can be favorable even when complete surgical margins are not obtained.