Effect of Experimentally Induced Synovitis on Amikacin Concentrations after Intravenous Regional Limb Perfusion


  • Work performed at the College of Veterinary Medicine, University of Georgia. Funded in part by 2008 Diplomate Clinical Research Grant awarded by the ACVS Foundation. Presented in part at the ACVS Veterinary Symposium, Washington, DC, October 8–10, 2009.

Corresponding Author

Axel M. Beccar-Varela, MV, Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Dr., Athens, GA 30602.

E-mail: varela@uga.edu



To determine the effects of experimentally induced synovitis of the radiocarpal joint on the intra-articular pharmacokinetics and pharmacodynamics of amikacin after intravenous regional limb perfusion (IVRLP).

Study Design

Randomized crossover experimental design.


Adult horses (n = 8).


Horses were randomly assigned into 2 trials: synovitis and no-synovitis. Radiocarpal joint synovitis was induced with lipopolysaccharide 6 hours before IVRLP. IVRLP (5-mg/kg amikacin qs 60 mL) was performed with a pneumatic tourniquet under general anesthesia. Synovial fluid was obtained before and 0.5, 1, 3, 5, 12, 24, 48 hours after IVRLP. Amikacin concentrations at each time point and pharmacokinetic values were compared between synovitis and no-synovitis trials with Student's t-test.


Amikacin synovial fluid concentrations indicated suspected tourniquet failure on 3 occasions (2 synovitis, 1 no-synovitis) on 3 different horses. Data from both trials in these 3 horses were excluded from further analysis. Observed time to maximal concentration (Tmax; mean ± SD = 54 ± 13.42 min) was reached earlier in synovitis joints (5/5, 30 min) than in no-synovitis joints (1/5, 30 min and 4/5, 1 h; P = .0476) (P = .0161). Mean observed maximal concentration (Cmax) was higher in synovitis joints (144.48 ± 43.17 μg/mL) than in no-synovitis joints (60.02 ± 28.81 μg/mL; P = .0301). The recommended Cmax: minimum inhibitory concentration ratio of 8 was achieved in 3/5 of the successfully perfused joints with induced synovitis, but this ratio was not achieved in any of the clinically normal joints.


Synovitis of the radiocarpal joint resulted in an earlier observed Tmax and higher observed Cmax of intra-articular amikacin after IVRLP compared with normal joints.