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Published on: August 30, 2018
Timing of Antimicrobial Prophylaxis and Tourniquet Inflation: A Randomized Controlled Microdialysis Study
Pelle Hanberg1,2, Mats Bue2, Kristina Öbrink-Hansen2
1Department of Orthopaedic Surgery, Horsens Regional Hospital, Horsens, Denmark.
Background:
Tourniquets are widely used during extremity surgery. In order to prevent surgical site infection, correct timing of antimicrobial prophylaxis and tourniquet inflation is important. We aimed to evaluate the time for which the free drug concentration of cefuroxime is maintained above the minimum inhibitory concentration (t > MIC) in porcine subcutaneous adipose tissue and calcaneal cancellous bone during 3 clinically relevant tourniquet application scenarios.
Methods:
Twenty-four female Danish Landrace pigs were included. Microdialysis catheters were placed bilaterally for sampling of cefuroxime concentrations in calcaneal cancellous bone and subcutaneous adipose tissue, and a tourniquet was applied to a randomly picked leg of each pig. Subsequently, the pigs were randomized into 3 groups to receive 1.5 g of cefuroxime by intravenous injection 15 minutes prior to tourniquet inflation (Group A), 45 minutes prior to tourniquet inflation (Group B), and at the time of tourniquet release (Group C). The tourniquet duration was 90 minutes in all groups. Dialysates and venous blood samples were collected for 8 hours after cefuroxime administration. Cefuroxime and various ischemic marker concentrations were quantified.
Results:
Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 µg/mL) in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet duration in Groups A and B. Cefuroxime administration at the time of tourniquet release (Group C) resulted in concentrations of >4 µg/mL for approximately of 3.5 hours in the tissues on the tourniquet side. Furthermore, tourniquet application induced ischemia (increased lactate:pyruvate ratio) and cell damage (increased glycerol) in subcutaneous adipose tissue and calcaneal cancellous bone. Tissue ischemia was sustained for 2.5 hours after tourniquet release in calcaneal cancellous bone.
Conclusions:
Administration of cefuroxime (1.5 g) in the 15 to 45-minute window prior to tourniquet inflation resulted in sufficient concentrations in calcaneal cancellous bone and subcutaneous adipose tissue throughout the 90-minute tourniquet application. Furthermore, tourniquet-induced tissue ischemia fully resolved 2.5 hours after tourniquet release.
Clinical Relevance:
Cefuroxime administration 15 to 45 minutes prior to tourniquet inflation seems to be a safe window. If the goal is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at the time of tourniquet release.
Insights
Administering cefuroxime 15–45 minutes before tourniquet use ensures effective drug levels for preventing surgical site infection. This timing maintains therapeutic cefuroxime concentrations in bone and tissue during procedures.
Area of Science:
- Pharmacology
- Surgical Infection Prevention
- Orthopedic Surgery
Background:
- Tourniquets are crucial in extremity surgery but pose infection risks.
- Optimal antimicrobial prophylaxis timing is vital for preventing surgical site infections.
- Cefuroxime's efficacy depends on maintaining concentrations above the minimum inhibitory concentration (MIC).
Purpose of the Study:
- To evaluate cefuroxime's time above MIC (t > MIC) in porcine bone and adipose tissue.
- To determine optimal cefuroxime administration timing relative to tourniquet application.
- To assess the impact of tourniquet use on tissue ischemia and cefuroxime concentrations.
Main Methods:
- Microdialysis catheters sampled cefuroxime in calcaneal bone and adipose tissue in 24 pigs.
- Pigs received 1.5g cefuroxime intravenously 15 min (Group A), 45 min (Group B) before, or at tourniquet release (Group C).
- Tourniquets were applied for 90 minutes; samples collected for 8 hours; ischemia markers quantified.
Main Results:
- Cefuroxime concentrations remained above the MIC for Staphylococcus aureus (4 µg/mL) throughout 90-minute tourniquet application in Groups A and B.
- Group C showed >4 µg/mL for ~3.5 hours post-release.
- Tourniquet application induced sustained ischemia and cell damage, resolving 2.5 hours after release in bone.
Conclusions:
- Administering cefuroxime 15–45 minutes pre-inflation maintains effective concentrations in bone and tissue for 90-minute tourniquet use.
- Tourniquet-induced ischemia resolved within 2.5 hours post-release.
- A second cefuroxime dose at tourniquet release may be needed to ensure sustained postoperative therapeutic levels.
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