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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 61 - 61
1 Dec 2021
Hanberg P Bue M Öbrink-Hansen K Thomassen M Sballe K Stilling M
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Aim

Tourniquet is widely used in 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 minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.

Method

Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 52 - 52
1 Dec 2021
Slater J Hanberg P Bendtsen MAF J⊘rgensen AR Greibe E Sballe K Bue M J⊘rgensen N Stilling M
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Aim

Pyogenic spondylodiscitis remains a therapeutic challenge, as demonstrated by divergent treatment guidelines. The combination of moxifloxacin and rifampicin may be an attractive treatment option for cases caused by staphylococci; however, previous studies have reported a reduction in plasma concentrations of moxifloxacin when co-administered with rifampicin. The magnitude of this reduction in spinal tissues is not known. We aimed to investigate the interaction of rifampicin on moxifloxacin tissue concentrations in vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue in steady-state conditions using microdialysis in a porcine model.

Method

Twenty female pigs were randomized into two groups of ten pigs: Group A received moxifloxacin 400 mg orally once daily for three days preoperatively. Group B received moxifloxacin 400 mg orally for three days preoperatively combined with rifampicin 450 mg twice daily for seven days preoperatively. Measurements were obtained from plasma, vertebral cancellous bone, intervertebral disc and subcutaneous adipose tissue for 24 h. Microdialysis was applied for sampling in solid tissues.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_5 | Pages 8 - 8
1 Mar 2021
Bendtsen MAF Bue M Hanberg P Slater J Thomassen M Hansen J Sballe K Öbrink-Hansen K Stilling M
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Aim

Flucloxacillin is conventionally administered intravenously for perioperative prophylaxis, while oral administration is typical for bacterial inoculation prophylaxis following smaller traumatic wounds. We aimed to assess the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT>MIC) for meticillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model.

Method

16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every 6 h during 24 h. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin fT>MIC was evaluated using a low MIC target (0.5 μg/mL) and a high MIC target (2.0 μg/mL).


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 91 - 91
1 Dec 2020
Hanberg P Bue M Öbrink-Hansen K Thomassen M Sballe K Stilling M
Full Access

Tourniquet is widely used in 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 minimal inhibitory concentration (T>MIC) in subcutaneous tissue and calcaneal cancellous bone during three clinically relevant tourniquet application scenarios.

Twenty-four female pigs were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in calcaneal cancellous bone and subcutaneous tissue, and a tourniquet cuff was applied on a randomly picked leg of each pig. Subsequently, the pigs were randomized into three groups to receive 1.5 g of cefuroxime by intravenous injection 15 min prior to tourniquet inflation (Group A), 45 min prior to tourniquet inflation (Group B), and at the tourniquet release (Group C). The tourniquet duration was 90 min in all groups. Dialysates and venous blood samples were collected eight-hours postcefuroxime administration.

Cefuroxime concentrations were maintained above the clinical breakpoint MIC for Staphylococcus aureus (4 μg/mL) in calcaneal cancellous bone and subcutaneous tissue throughout the 90 min tourniquet duration in Group A and B. Cefuroxime administration at tourniquet release (Group C) resulted in concentrations above 4 μg/mL for a minimum of 3.5 hours in the tissues on the tourniquet side. There were no significant differences in the T>MIC (4 μg/mL) in subcutaneous tissue or calcaneal cancellous bone between the three groups. However, Group A tended toward shorter T>MIC in tourniquet calcaneal cancellous bone compared to Group C (p=0.08).

We conclude that administration of cefuroxime (1.5 g) in the 15–45 min window prior to tourniquet inflation resulted in sufficient calcaneal cancellous bone and subcutaneous tissue concentrations throughout the 90 min tourniquet application. If the target is to maintain postoperative cefuroxime concentrations above relevant MIC values, our results suggest that a second dose of cefuroxime should be administered at tourniquet release.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_11 | Pages 92 - 92
1 Dec 2020
Hanberg P Bue M Kabel J J⊘rgensen AR Jessen C Sballe K Stilling M
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Tourniquet is widely used in orthopedic surgery to reduce intraoperative bleeding and improve visualization. We evaluated the effect of tourniquet application on both peri- and postoperative cefuroxime concentrations in subcutaneous tissue, skeletal muscle, calcaneal cancellous bone, and plasma. The primary endpoint was the time for which the free drug concentration of cefuroxime was maintained above the clinical breakpoint minimal inhibitory concentration (T>MIC) forStaphylococcus aureus (4 µg/mL).

Ten patients scheduled for hallux valgus or hallux rigidus surgery were included. Microdialysis catheters were placed for sampling of cefuroxime concentrations bilaterally in subcutaneous tissue, skeletal muscle, and calcaneal cancellous bone. A tourniquet was applied on the thigh of the leg scheduled for surgery. Cefuroxime (1.5 g) was administered intravenously as a bolus 15 minutes prior to tourniquet inflation, followed by a second dose 6 hours later. The mean tourniquet duration (range) was 65 (58; 77) minutes. Dialysates and venous blood samples were collected for 12 hours.

For cefuroxime the T>MIC (4 μg/mL) ranged between 4.8–5.4 hours across compartments, with similar results for the tourniquet and non-tourniquet leg. Comparable T>MIC and penetration ratios were found for the first and second dosing intervals.

We concluded that administration of cefuroxime (1.5 g) 15 minutes prior to tourniquet inflation is safe in order to achieve tissue concentrations above 4 µg/mL throughout surgery. A tourniquet application time of approximately 1 hour did not affect the cefuroxime tissue penetration in the following dosing interval.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 80 - 80
1 Dec 2019
Thomassen M Hanberg PE Stilling M Kjær K Sballe K Krag L H⊘jskov C Bue M
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Aim

Local treatment with gentamicin may be an important tool in the prevention and treatment of surgical site infections in high-risk procedures and patients. The aim of this study was to evaluate the pharmacokinetic profile of gentamicin in bone and surrounding tissue, released from a controlled application of a GentaColl sponge in a porcine model.

Method

In 8 female pigs, a GentaColl sponge of 10×10 cm (1.3 mg gentamicin/cm2) was placed in a cancellous bone cavity in the proximal tibia. Microdialysis was used for sampling of gentamicin concentrations over 48 hours from the cavity with the implanted GentaColl sponge, cancellous bone parallel to the cavity over and under the epiphyseal plate, cortical bone, the intramedullary canal, subcutaneous tissue, and the joint cavity of the knee. Venous blood samples were obtained as reference.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 320 - 320
1 Mar 2004
Kold S Rahbek O Zippor B Overgaard S S¿balle K
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Introduction/Aims: Initial implant stability is crucial for long-term implant survival. A new surgical technique, compaction, has increased in vivo stability of implants inserted with pressþt. However, gaps often exist in total joint replacements between the implant bone bed and the implant. Therefore, we examined in a gap model whether the compaction technique would increase þxation of hydroxylapatite (HA) implants when compared with the conventional drilling technique. Methods: HA coated titanium implants (diameter 6 mm) were inserted bilaterally in the proximal humerus of 7 dogs for 2 weeks. The implant cavity was randomized to either drilling with an 8 mm drill or to compaction by radial enlarging an initial 5 mm drill hole to 8 mm. Implants were tested to failure by push-out test, and histomorphometry was performed. Data are presented as medians with interquartile range in brackets. The Wilcoxon Signed Ranked Test tested differences between compaction and drilling. P-values < 0.05 were considered signiþcant (*).

Conclusion: In this gap model, compaction signiþcantly increased mechanical and histological þxation of HA coated implants.


Orthopaedic Proceedings
Vol. 86-B, Issue SUPP_III | Pages 366 - 367
1 Mar 2004
Elmengaard B Bechtold J S¿balle K
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Aims: Early bone ingrowth is known to increase primary implant þxation and reduce the risk of early implant failure. RGD peptide (Arg-Gly-Asp) has been identi-þed as playing a key role in osteoblast attachment and proliferation on various surfaces. The aim of this study is to test whether a monolayer of RGD peptide on Ti implants will increase bone ingrowth in vivo. Methods: Controlled canine study (n=8). 6 x 10mm plasma sprayed porous coated implants (Ti6Al4V) was inserted as press-þt in the proximal tibia bilaterally. Observation period was 4 weeks. Implants was coated in a 100 μM solution of cylic (RGDfK) peptide for 24 hours (Biomet-Merck, Darmstadt, Germany). Two dogs had to be excluded due to wrong placement of the implants. Results are presented as median and range. Results: A signiþcant increase in bone/implant contact was seen for the RGD treated group (p< 0.05). Bone fraction at the interface was 0.18 (0.10–0.45) compared to 0.09 (0.05–0.14) for the control. Mechanical þxation, measured by push-out test, was increased. Shear strength was 85% higher for the RGD group; however this difference was not signiþcant. Conclusions: This study shows that implant surface treatment with RGD enhances early bone ingrowth to press-þtted implants. However, future studies will be preformed regarding coating integrity and long-term effects, as well as its performance under loaded conditions.