Does Cyclical Loading Affect Antibiotic Elution and Strength of Articulating Cement Knee Spacers?

BA Rogers1, F Middleton2, N Shearwood-Porter3, S Kinch3, A Roques4, N Bradley5, A Taylor4, M Browne3

1.

Mount Sinai Hospital, Toronto Kingston Hospital, UK

3.

School of Engineering Sciences, University of Southampton, UK Aurora Orthopaedics, UK 5. Royal Surrey County Hospital, UK.

2.

4.

Study Rationale
To date, little known on how cyclical fatigue loading affects antibiotic elution from cement spacers

Aim
To compare the differential effect of antibiotics on in-vitro elution with static or dynamic loading

Null hypothesis
Cyclical loading of cement spacers has no significant effect on antibiotic elution

Sample Preparation
Hand mixed Palacos R bone cement Biomet Stage One 70mm silicon spacer moulds

Methodology: Specimen Preparation

Concentration Low Medium High Mass of Vancomycin per 40g cement 1g 1g 1g Mass of Tobramycin per 40g cement 1.2g 2.4g 3.6g

4 spacers for each concentration of antibiotics were made for dynamic loading Two spacers for each concentration were made as controls Immersed in Phosphate buffered solution (PBS) 5ml samples of PBS taken over a set 48 hr schedule

Methodology: Dynamic Loading

Methodology: Sampling Rate

Time Elapsed Test 5 minutes 2 hours 4 hours 6 hours 22 hours 24 hours 26 hours 28 hours

No. of cycles Control 0 0 0 0 0 0 0 0 0 0 7000 14000 14000 21000 28000 35000

Knee spacers immersed in solution; 3 x 5ml samples taken as per schedule Measurement of antibiotic elution by ELISA

Vancomycin Elution Control Group

Rapid initial release Levelling of concentration after ~ 400mins Vancomycin elution increases with increasing dose of tobramycin

Tobramycin Elution Control Group

Similar profile Tobramycin elution increases with increasing dose of tobramycin

Dynamic Results:
Low Concentration

1.0g Vancomycin, 1.0g Tobramycin

Vancomycin Release

Tobramycin Release

Dynamic Results:

1.0g Vancomycin,

2.4g Medium Concentration Tobramycin

Vancomycin Release

Tobramycin Release

Dynamic Results:
High Concentration

1.0g Vancomycin, 3.6g Tobramycin

Vancomycin Release

Tobramycin Release

Discussion
This study confirms..
Static & Dynamic Spacers Standard elution pattern : rapid initial antibiotic release steady state release at 400mins

Increasing tobramycin in cement enhances vancomycin elution enhances tobramycin elution

Discussion
This study adds Cyclical loading increases antibiotic elution P<0.05 (ANOVA) Tobramycin potentiates effect of cyclical loading Dose-related manner

Discussion
Masri et al1, found significant increase in static elution of vancomycin when dose of tobramycin was increased Penner et al2, propose passive opportunism; whereby antibiotics elute by leaking out from voids and cracks. Tobramycin - increases void formation, and thus increasing elution Need further results to investigate this
1. Masri et al, 1998, J. Arthrop., 13(3), 331-338 2. Penner et al, 1996, J. Arthrop., 11(8), 939-944

Null hypothesis
In vitro cyclical loading of cement spacers has no significant effect on antibiotic elution

Refute for Tobramycin and Vancomycin, with statistical significance (p<0.05, ANOVA)

Conclusion
Dynamic Cement Spacers Mechanical and soft tissue benefits well known This study provides evidence for the biological benefit of articulating cement spacers in revision surgery Future work zirconium dioxide replaced by CaCO3 Different antibiotic combinations or anti-fungals? Load to failure & cement porosity

Thank You
Acknowledgements