Experimental Research To Study Elution Characteristics Of Antibiotic Loaded PMMA Rod Implanted In A Rabbits Model

Objective: Implanted antibiotic loaded PMMA rod into proximal femoral medullary cavity of rabbits by surgical operation, observed elution characteristics of PMMA rods in vivo, and obtained local antibiotic time-concentration curve.Methods: 0.5/1.0/1.5/2.0g norvancomycin was mixed respectively and thoroughly with 20 g dry Polymethylmethacrylate powder. An appropriate weight of liquid methylmethacrylate monomer was added into the powder mixture. The mixture was rolled into rods with a uniform mould when it was pliable. After curing at room temperature, each rod was sterilized with ethylene oxide gas. Before operation, the animals were placed into individual rabbit cages and allowed free access to food and water for 3 days. 16 male rabbits were randomly divided into 4 groups. They were anesthetized with 2% sodium pentobarbital(1.5ml/Kg) through injected marginal ear vein. The left hind leg was shaved and prepared using povidone and iodine solution. 4cm incision was taken. Then the proximal femur was demonstrated between temoriss and musculi biceps femoris. A longitudinal trough of 2cm was fashioned in the proximal femur using a rongeur carefully. The antibiotic loaded PMMA rod was inserted into the medullary cavity of femur and fixed using no absorbable sutures. And then drainage device was placed under the muscle. Taken samples of drainage intramedullary at 1、2、5、8、12、17、23、28d postoperatively and serum from marginal ear vein at 1、2、3、7、15、28d postoperatively. Concentrations of norvancomycin from sample were gauged by high performance liquid chromatography after centrifugal separation.Results: All rabbits were alive during the period of experiment. No intraoperative or postoperative complications occurred, and all operative sites healed normally. Local concentrations of norvancomycin reached peak value at the second day postoperatively(Group 1:120.33±19.97μg/m L;Group 2:77.70±12.99μg/m L; Group 3 : 50.25±8.80μg/m L; Group 4 :33.38±9.99μg/m L),and began decreased slowly. Concentrations eluted from high proportion antibiotic were higher than the other groups significantly. Experimental result was made analysis of variance for repeated measurement data. There are differences within concentrations eluted from groups which had different proportion of antibiotic in PMMA( P<0.05) There are differences within changing trend of each group(P<0.05).Conclusion: Local norvancomycin concentrations eluted from PMMA bone cement were upper than minimum inhibitory concentration of norvancomycin sensitivity of the pathogenic bacteria during the period of experiment. Systemic level of norvancomycin was well below the concentration associated with toxicity and undetected late in the experiment. The experiment result show that norvancomycin loaded PMMA bone cement could release high concentration of antibiotic as a local drug delivery device in a certain period of time and system level could maintain in the safe range.