Evaluation of haemodialysis as a protective technique for preventing high daily dose amikacin nephrotoxicity: an experimental study in an ovine model.

Changes in pharmacokinetic parameters of critically ill patients make the treatment of infections challenging, particularly when multidrug-resistant bacteria are involved. The aim of this study was to evaluate the ability of haemodialysis to reduce the exposure to high dose amikacin and prevent nephrotoxicity. Amikacin 50 mg/kg was administered intravenously to six adult sheep once-daily for four days. The sheep were divided into two groups according to the implementation (group 1) or not (group 2) of haemodialysis. In group 1, haemodialysis was performed for 4 h, initiated 2 h after starting amikacin infusion. Amikacin area under the curve (AUC) and trough concentrations (Cmin) were used as markers of amikacin-induced nephrotoxicity. The median haemodialysis amikacin clearance was 2.14 L/h (35.6 mL/min), 14% of the mean total body clearance for 24 h. Haemodialysis reduced Cmin (group 1: 0.3 µg/mL [0.3-1.1]; group 2: 1.4 µg/mL [1.1-3.9]; P = 0.0003). A trend towards reduced AUC with haemodialysis was observed (group 1: 1450 µg/mL⋅h [1311-1716]; group 2: 3126 µg/mL⋅h [2581-3171]; P = 0.10). In conclusion, haemodialysis seems interesting in reducing AUC and Cmin after the injection of high-dose of amikacin, parameters known to be involved in its induced nephrotoxicity, in an experimental ovine model.