|Titel på arbejdet
|Peri- and Post-operative Influence of Tourniquet Application on Cefuroxime Tissue Concentrations and Tissue Ischemia
|Afdeling / Sted
|Ortopædkirurgisk afdeling, Regionshospitalet Horsens
|Abstract / Summary
Tourniquets are widely used in orthopaedic surgery due to their ability to reduce intraoperative bleeding and improve visualisation. However, as the blood supply to the operating field is occluded during surgery, correct timing of antimicrobial prophylaxis administration and tourniquet inflation is essential in order to ensure therapeutic tissue concentrations at the surgical site. Currently, the guidelines are ambiguous.
Tourniquet use has been associated with multiple adverse effects, including longer recovery time, reduced muscle strength, soft tissue damage and slow wound healing. Although many of these adverse effects may be related to tourniquet-induced ischemia, only a few studies have investigated local tissue metabolite changes during and after tourniquet application.
The overall objective of this PhD project was to validate and apply microdialysis in order to evaluate the effects of tourniquet application on both peri- and post-operative cefuroxime and ischemic metabolite concentrations in orthopedically-relevant tissues. These objectives were evaluated in a three-step approach: (1) in vitro and in vivo evaluation of the microdialysis calibration method used, (2) an experimental in vivo study evaluating different timepoints for cefuroxime administration and tourniquet inflation, and lastly, (3) a clinical study evaluating the effects of tourniquet application on cefuroxime and ischemic metabolite tissue concentrations peri- and post-operatively over two dosing intervals. The design of each individual step in this three-step approach was reliant on the preceding findings.
Meropenem was validated as a suitable internal standard for cefuroxime, and microdialysis was successfully applied to evaluate cefuroxime and ischemic metabolite tissue concentrations before, during and after tourniquet application. Administering 1.5 g cefuroxime 15–45 min prior to tourniquet inflation was found to be a safe window in order to achieve bone and soft tissue concentrations above 4 μg/mL, and a tourniquet application time of approximately 60 min did not affect the cefuroxime tissue concentrations in the following dosing interval. Furthermore, a tourniquet-application time of approximately 60–90 min was found to induce only limited tissue ischemia and cell damage in cancellous bone and soft tissues.