The clinical guidelines for hip fracture management indicate that indwelling foley catheterization should be avoided when possible. Alternatives to indwelling catheters such as intermittent or condom catheters are recommended. Appropriate catheterization usage is important in hip fracture patients to avoid complications such as urinary tract infections (UTIs) (7–24% of patients) or post-operative urinary retention (POUR) (20–56% of patients). In this study, we aim to, (1) evaluate catheter usage in hip fracture patients at a large tertiary care centre, (2) compare current practices in catheter usage to clinical guidelines, (3) determine the incidence of POUR in hip fracture patients (4) determine the factors that increase one's risk of developing POUR. We analyzed 584 hip fracture patients between the ages of 18 and 102 admitted between November 2015 and October 2017 at a tertiary Care Hospital. Data collected included patient demographics, fracture pattern, surgical procedure, length of stay, co-morbidities and catheter use. We compared actual catheter usage to suggested guidelines to determine whether recommendations were being followed. We also investigated the incidence of POUR and risk factors associated with developing POUR. Independent samples t-test were used to compare continuous dependent variables in bivariate analyses and a logistic regression was used to determine predictors of developing POUR, catheter usage, and length of stay in multivariate analyses. T. Over three quarters (76.9%) of patients with hip fractures were treated with a catheter during their admission, 63.5% of which were inserted pre-operatively and 36.5% of which were inserted post-operatively. Indwelling catheters accounted for 92.2% of catheters used, while intermittent and catheter condoms accounted for 7.8%. POUR occurred in 98 of 584 cases (16.7%). Age (p = 0.004), gender (p=0.001), and presence of kidney disease (p=0.033) were statistically significant predictors of POUR. Fracture pattern (p=0.825), surgical procedure (p=0.298), diabetes mellitus (p=0.309) and UTI in the past 60 days (p=0.848) or on admission (p=0.999) were not statistically significant predictors of developing POUR. The development of POUR did not significantly increase length of stay (p=0.558). There was no statistically significant correlation between developing POUR and extended post-operative catheter use over 24 hours (p=0.844) or 48 hours (p=0.862). Patients who received a catheter pre-operatively or post-operatively for longer than 24 hours were not significantly more likely to develop POUR (p=0.057). Catheter use was common for all hip fracture patients and indwelling catheters were used in the overwhelming majority of cases. The high frequency of catheter usage, and specifically indwelling catheter usage, suggests that there is low compliance with the clinical guidelines for hip fracture patients. The incidence of POUR was 17%. Older, male patients were more likely to develop POUR. Although not statistically significant, more appropriate catheter use may decrease urinary complications such as POUR

Aim. The objective of this systematic review is to evaluate the current evidence for or against this up-and-coming treatment modality. Method. A comprehensive literature search in accordance with the Preferred Reporting Items for Systematic review and Meta-analysis (PRISMA) guidelines was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Exclusion criteria included patients < 18 years of age, follow-up <11 months, and a score < 6 on the National Institute of Health quality assessment tool. Results. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The quality of many studies was impeded by a retrospective design (14/15), a relative small study population (10 out of 15 studies had less than 50 patients), selection bias, and remarkable heterogeneity in terms of catheter type, antibiotic type, dose and duration of IA antibiotics and techniques of surgical revision. 347 were chronic infections, 66 acute infections and 218 unknown. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (499/631, 79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (77/631, 12.2%), DAIR with adjuvant IA antibiotic infusion (36/631, 5.7%) or two-stage revision with adjuvant IA antibiotic infusion (19/631, 3.0%). Mean duration of IA antibiotic infusion was 19 days (range 3–50), although most patients received a combination of both IA and systemic (IV or PO) antibiotics. An overall failure rate (defined as failures of infection eradication/total PJIs) of approximately 11% was found. The use of IA antibiotic infusion as a stand-alone treatment was associated with a higher failure rate. In total 117 complications occurred in 631 cases (18.5%). Of these, 71 were non-catheter-related (60.7%) and 46 were catheter-related (39.3%). The most common catheter-related complications were premature loss of the catheter (18/46), developing a fistula (5/46), and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Conclusions. Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. From a theoretical point of view it seems likely that is should not be used as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs, labour and catheter-related complications of this treatment modality

Purpose. Femoral nerve blockade (FNB) can provide prolonged postoperative analgesia and facilitate rehabilitation following major knee surgery while minimizing opioid-related adverse effects. However, anecdotal data have implicated FNB in post-operative falls, presumably due to a block-related reduction in quadriceps strength. Age, gender and knee replacement surgery have also been previously identified as risk factors for falls in the acute postoperative orthopaedic inpatient setting. We hypothesized that the use of FNB would be an independent predictor of an inpatient fall following total knee replacement (TKR). Method. We examined a cohort of 2,197 patients who underwent TKR in a single academic institution between October 2003 and March 2010. The start date was based on the separate initiation of both a comprehensive regional anesthesia database and an orthopaedic ward Falls Surveillance Program. Patients undergoing revision TKR or unicompartmental arthroplasty were excluded. Age, simultaneous bilateral TKR, gender, body mass index (BMI), and various regional nerve blocks were considered predictors of post-operative falls in a logistic regression model. The database allowed resolution of the type (i.e. femoral, sciatic) and duration (i.e. single-bolus, indwelling continuous perineural catheter) of nerve blockade. Hospital-standard dosing and insertion techniques were employed. Results. The total number of falls was 60 (rate 2.7%), 40 of which occurred within 48 hours of surgery. When compared to patients who did not fall, those who fell were significantly older (699 years vs 6611 years; p=0.03), obese [BMI >30kg/m2] (75% vs 59%; p=0.01) and had continuous catheter FNB (97% vs 86%; p=0.02). The odds ratio of having a fall was 1.04 (1.0–1.07; p=0.008) for each one-year increase in age above the mean age of 66 years, 2.4 (1.3–4.5; p=0.005) for a BMI >30kg/m2 and 4.4 (1.04–18.2; p=0.04) for continuous catheter FNB. Gender, simultaneous bilateral TKR, any sciatic nerve block or spinal anesthetic did not predict an increased risk of acute-care post-operative falls. Conclusion. This is the first study to demonstrate an increased risk of post-operative falls in obese patients and with the use of continuous catheter FNB following TKR. Careful consideration of the use of continuous catheter FNB may be warranted in patients with additional risk factors for falls such as advanced age and obesity

Prevention and treatment of total joint infection is closely related to biofilm formation and concentration of antibiotics achieved in the area around the implants. Most total joint infections are caused by bacteria that enter the wound at the time of the operation. These bacteria can attach to surfaces and rapidly form biofilm that is highly resistant to antibiotics. Prophylactic antibiotics given intravenously achieve concentration of local antibiotics in the knee in response to intravenous antibiotics about 1/3 of that achieved in the serum, and the level is transient. This may be enough to treat the planktonic form of the bacteria, but far from enough to treat the biofilm. The concentration of antibiotics in the joint fluid achieved with antibiotics applied locally during surgery is 1000 times higher, and can be maintained throughout the procedure. High concentration persists in drainage fluid for 24 hours after surgery. Studies done with use of local antibiotics in spinal implant surgery indicate a major reduction in the rate of infection, and cost analysis shows remarkable monetary benefit to this effect.

Infected total joints benefit especially from direct application of antibiotics to the local area. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were thousands of times higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours.

Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics.

Preventing and treating infection in orthopaedic implant surgery requires achieving concentrations that are above the minimal biofilm eradication concentration. This can be achieved only with direct application.

In patients admitted to hospital with a hip fracture, urinary issues are common. Despite guidelines that recommend avoiding foley catheter usage when possible, it remains a common part of perioperative care. To date, there is no prospective data on the safety and satisfaction associated with catheter use in such cohort. The aim of this study was to evaluate the satisfaction of patients when using a foley catheter while they await surgery for their fractured hip and the safety associated with catheter use. In our prospectively collected database, 587 patients were admitted to our tertiary care center over a 1 year period. Most patients (328) were catheterized within the first 24h of admission, primarily inserted in ED. Of these patients, 119 patients (61 catheterized and 58 noncatheterized) completed a questionnaire about their perioperative management with foley catheter usage administered on day 1 of admission. This was used to determine satisfaction of catheter use (if catheterized) and pain levels (associated with catheterized or associated with transferring/voiding if not catheterized). Adverse effects related with catheter use included urinary tract infection (UTI) and post-operative urinary retention (POUR). Ninety-five percent of patients found the catheter to be convenient. Only 5% of patients reported any pain with catheter use. On the contrary, 47.5% of non-catheterized patients found it difficult to move to the bathroom and 30.4% found it difficult to urinate. Catheterized patients had significative less pain than uncatheterized patients (0.62/10 vs 2.45/10 respectively, p < 0 .001). The use of nerve block reduced pain levels amongst catheterized patients but was not associated with reduced pain levels or satisfaction amongst non-catheterized patients. The use of catheter was not associated with increased risk of UTI(17.5% in the catheterized vs 13.3% in the non-catheterized, p = 0.541) or POUR (6.8% in the catheterized vs 11.1% in the non-catheterized, p = 0.406). This study illustrates the benefits and safety associated with the use of urinary catheters in the pre-operative period amongst hip fractures. The use of catheters was associated with reduced pain and satisfaction without increasing post-operative UTI or POUR. These findings suggest that pre-operative catheter use is associated with less pain and more satisfaction for patients awaiting hip surgery and whom other measures, such as nerve blocks, are unlikely to reduce the discomfort associated with the mobility required to void. A prospective randomized control study could lead to a more evidence based approach for perioperative foley catheter usage in hip fracture patients

Aim. Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). Method. In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). Results. During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. Conclusions. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Acknowledgments. We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study. This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020]

Aim. Antibiotic prophylaxis is central in preventing postoperative spine infections, yet knowledge of clinical spine tissue antibiotic concentrations remains limited. Pooled postoperative spine infection rates are constant (approximately 3%), resulting in severe patient morbidity, mortality, and prolonged hospitalization. Current antibiotic dosing regimens often involve fixed doses based on empirical knowledge, surrogate measures (plasma samples), non-clinical evidence (experimental models), and inferior methodology (tissue specimens). Therefore, personalized antibiotic dosing may be the future of antibiotic prophylaxis to prevent postoperative infections, especially implant infections. The aim was to continuously evaluate intra- and postoperative cefuroxime target spine tissue concentrations in long-lasting spine surgery after personalized dosing by repeated weight-dosed intravenous administrations. Method. Twenty patients (15 female, 5 male) scheduled for long-lasting spine deformity surgery with hypotensive anaesthesia were included; median age (range): 17.5 years (12-74), mean BMI (range): 22.2 (16.2-37.7), and mean surgery time (range): 4h 49min (3h 57min-6h 9min). Weight-dosed cefuroxime (20 mg/kg) was administered intravenously to all patients on average 25 min before incision and repeated after 4 hours. Microdialysis catheters were placed for sampling of cefuroxime concentrations in vertebral bone (only intraoperative sampling), paravertebral muscle, and subcutaneous tissue as soon as possible after surgery start. Upon wound closure, two additional catheters were placed in the profound and superficial part of the wound. Microdialysis and plasma samples were obtained continuously intra- and postoperative for up to 12 hours. The primary endpoint was (based on cefuroxime time-dependent efficacy) the time with cefuroxime concentrations above the clinical breakpoint minimal inhibitory concentration for Staphylococcus aureus of 4 µg/mL in percentage (%fT>MIC4) of. (a). patients’ individual surgery time,. (b). first dosing interval (0-4 hours),. (c). second dosing interval (4-12 hours). Results. Mean cefuroxime %fT>MIC4 (range) of:. (a). patients’ individual surgery time was 100% (100-100%) in all investigated tissues. (b). the first dosing interval was 93% (93-93%) in vertebral bone, paravertebral muscle, subcutaneous tissue, and 99% (99-100%) in plasma. (c). the second dosing interval was 87% (52-100%) in paravertebral muscle, 89% (52-100%) in subcutaneous tissue, 91% (71-100%) in the profound wound, 94% (72-100%) in the superficial wound, and 71% (42-100%) in plasma. Conclusions. Personalized cefuroxime dosing by repeated weight-dosed (20 mg/kg) intravenous administrations provided homogenous and therapeutic spine tissue exposure across all investigated tissues and plasma in long-lasting spine surgery with hypotensive anaesthesia (up to 11 hours). Thus, personalized cefuroxime dosing may decrease the risk of postoperative spine infection, especially in cases with implant insertion

Aim. To develop a new system for antibacterial coating of joint prosthesis and osteosynthesis material. The new coating system was designed to release gentamicin immediately after insertion to eradicate surgical contamination. Method. Steel implants (2×15mm) were coated with a solid nanocomposite xerogel made from silica and the dendritic polymer, hyperbranched polyethyleneimine. The xerogel was anchored inside a porous surface made by pre-coating with titanium microspheres. Finally, gentamicin was encapsulated in the xerogel, i.e. no chemical binding. A total of 50 µg gentamicin was captured into each implant. The efficacy of the new coating was evaluated in a porcine model of implant associated osteomyelitis. In total, 30 female pigs were randomized into 3 study groups (n=10). Group A; plain implants + saline, Group B; plain implants + 10. 4. CFU of Staphylococcus aureus, and Group C; coated implants + 10. 4. CFU of S. aureus. Implant + inoculum was placed into a pre-drilled implant cavity of the right tibia and the pig was euthanized 5 days afterwards. Postmortem microbiology and pathology were performed. Two additional pigs were used in a pharmacokinetic study where microdialysis (MD) catheters were placed alongside coated implants. Extracellular fluid was sampled regularly for 24 hours from the MD catheters and analyzed for gentamicin content. Results. Within Groups A and C, all implants were found sterile by sonication and bacteria could not be identified within the surrounding bone tissue. In contrast, all Group B animals had S. aureus positive implant and tissue microbiology. Macroscopic and microscopic pathological examinations confirmed that Group A and C animals were complete identic, i.e. no pus around implants and only minor peri-implant inflammation related to insertion of implants per se. All Group B animals had pus around their implants and a massive peri-implant inflammatory response dominated by neutrophil granulocytes. Maximum gentamicin release (35 µg /mL) was measured in the first obtained MD sample, i.e. after 30 min, and the concentration stayed above the MIC level for the used S. aureus strain for 8 hours. Conclusions. The new xerogel coating prevented development of osteomyelitis. Prevention was due to a fast gentamicin release immediately following insertion and antimicrobial active concentrations were detectable several hours after implantation. This means that the critical time point of most relevant surgical procedures potentially could be protected by the novel coating. The new coating will be investigated on larger scale implants and full-size prosthesis in the future

Chronic postsurgical pain (CPSP) can occur after elective mid/hindfoot and ankle surgery. Effective treatment approaches for CPSP in this population have not been extensively investigated. The impact of multimodal strategies on CPSP following elective mid/hindfoot surgery is unknown due to both the heterogeneity of acute pain management and the lack of a recognized definition specific to this type of surgery. This study aimed to identify and evaluate current pain management strategies after elective mid/hindfoot and ankle surgery. We conducted a systematic review under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three databases (MEDLINE, Embase and Cochrane Library) were electronically searched for English studies published between 1990 and July 2017. Reference lists of relevant systematic reviews were also manually searched. Comparative studies of adults undergoing elective mid/hindfoot and ankle surgery were included. Two reviewers independently reviewed studies and assessed their methodological quality. Of 1,159 studies, seven high-quality randomized controlled trials met our inclusion criteria. Though all studies examined regional anesthesia techniques, intervention heterogeneity precluded meta-analysis. Participants were typically followed up to 48 hours post-operatively. Interventions effective at reducing postoperative pain and/or opioid consumption included inserting popliteal catheters under ultrasound instead of nerve stimulation guidance, infusing perineural dexamethasone, bupivacaine, or ropivacaine perioperatively, and adding a femoral catheter infusion to a popliteal catheter infusion. Only one study assessed pain six months following elective mid/hindfoot and ankle surgery, demonstrating significant pain reduction with activity with the addition of a femoral to popliteal catheter infusion. There is an overwhelming lack of evidence regarding CPSP and its management for patients undergoing elective mid/hindfoot and ankle surgery. Although specific regional anesthesia techniques and adjuncts may be effective at reducing in-hospital pain and opioid consumption after elective mid/hindfoot and ankle surgery, our systematic review identified only seven studies addressing multimodal pain management in this population. Further comparative studies with longer-term follow-up are required

Background and aim. Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low it is crucial to achieve adequate antibiotic concentrations proximate to the implant for a sufficient amount of time to protect the implant surface and ensure tissue integration. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant inserted in cancellous bone. Method. Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12–18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. Results. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). For the low piperacillin target (8 μg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54–74%) was found. For the high target (16 μg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49–54%), and similar between the two cancellous bone compartments. Conclusions. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered

Chronic postoperative pain (CPP) can occur in elective mid/hindfoot and ankle surgery patients. Multimodal pain management has been reported to reduce postoperative pain and opioid use, which may prevent the development of CPP. However, few studies have examined the impact of multimodal pain management strategies on CPP following complex elective mid/hindfoot and ankle surgery. The purpose of this study was to 1) evaluate current pain management strategies and 2) determine current definitions, incidence, and prevalence of CPP after elective mid/hindfoot and ankle surgery. Three databases (MEDLINE, Embase and Cochrane Library) were manually and electronically searched for English language studies published between 1990 and July 2017. For the first aim, we included comparative studies of adults undergoing elective mid/hindfoot and ankle surgery that investigated pre-, peri- or postoperative pain management. For the second aim, we included observational studies examining CPP definition, incidence, and prevalence. Two reviewers independently screened titles and abstracts, followed by full texts. Conflicts were resolved through discussion with a third reviewer. Reviewers also independently assessed the quality of studies meeting inclusion criteria using the Joanna Briggs Institute Critical Appraisal Checklist. For the first aim, 1159 studies were identified by the primary search, and seven high quality randomized controlled trials were included. Ankle arthroplasty or fusion and calcaneal osteotomy were the most common procedures performed. The heterogeneity of study interventions, though all regional anesthesia techniques, precluded meta-analysis. Most investigated continuous popliteal, sciatic and/or femoral nerve blockade. Participants were typically followed up to 48 hours postoperatively to examine postoperative pain levels and morphine consumption in hospital. Interventions effective at reducing postoperative pain and/or morphine consumption included inserting popliteal catheters using ultrasound instead of nerve stimulation guidance, perineural dexamethasone, and adding continuous femoral blockade to continuous popliteal blockade. Using more than one analgesic was generally more effective than using a single agent. Only two studies examined longer term pain management. One found no difference in pain levels and opioid consumption at two weeks with perineural or systemic dexamethasone use. The other found that pain with activity was significantly reduced at six months postoperatively with the addition of a femoral catheter infusion to a popliteal catheter infusion. For the second aim, only two studies of the 747 identified were selected. One prospective observational study defined CPP as moderate-to-severe pain at one year after foot and ankle surgery, and reported 21% and 43% of patients as meeting their definition at rest and with activity, respectively. The other study was a systematic review that reported 23–60% of patients experienced residual pain after total ankle arthroplasty. There is no standardized definition of CPP in this population, and incidence and prevalence are rarely reported and vary largely based on definition. Although regional anesthesia may be effective at reducing in-hospital pain and opioid consumption, evidence is very limited regarding longer-term pain management and associated outcomes following elective mid/hindfoot and ankle surgery

Aim. Prompt and sufficient broad spectrum empirical antibiotic treatment is key to prevent infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off minimal inhibitory concentrations (T>MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC-targets were applied: 1 and 4 µg/mL for vancomycin and 0.125 and 2 µg/mL for meropenem. Materials and methods. 8 pigs received a single dose of 1000 mg vancomycin and 1000 mg meropenem simultaneously over 100 min and 10 min, respectively. Microdialysis catheters were placed for sampling over 8 h in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted epidemiological cut-off values, vancomycin displayed longer T>MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T>MIC. For the low MIC targets and across compartments, T>MIC ranged between 208–499 min (46–100%) for vancomycin and 189–406 min (42–90%) for meropenem. For the high MIC targets, T>MIC ranged between 30–446 min (7–99%) for vancomycin and 45–181 min (10–40%) for meropenem. Conclusion. The differences in the T>MIC between the low and high targets illustrates how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contaminating or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T>MIC in all the exposed tissues and thereby lowering the risk of acquiring an infection after open tibial fractures

Aim. The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model. Method. 12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied. Results. For all investigated MIC targets, IV penicillin G resulted in a longer mean fT>MIC in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral penicillin V. Across compartments, mean fT>MIC for IV penicillin G (MIC: 0.125, 0.25 and 0.5μg/mL) were ≥97%, ≥84% and ≥75% during the first dosing interval, and 100%, ≥95% and ≥88%, during the third dosing interval. The mean fT>MIC for oral penicillin V were ≥40%, ≥24% and ≥7% during the first dosing interval, and ≥42%, ≥36% and ≥18% during the third dosing interval. Conclusions. The findings suggest that standard clinical dosing of IV penicillin G provides superior fT>MIC in cancellous bone and subcutaneous tissue compared to oral penicillin V, particularly in the third dosing interval. This emphasizes the importance of appropriate route of administration when applying penicillin treatment. Acknowledgements. Funding was received from The Kirsten and Freddy Johansen Foundation, The Novo Nordisk Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, King Christian the 10. th. Foundation, The A.P. Møller Foundation, The Dagmar Marshalls Foundation, and The Carl and Ellen Hertz Foundation

Background. Surgical site infection following spine surgery is associated with increased morbidity, mortality and increased cost for the health care system. The reported pooled incidence is 3%. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and often involve the lumbar spine. Accordingly, the objective was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column of the same lumbar vertebra using microdialysis in an experimental porcine model. Method. The lumbar vertebral column was exposed in 8 female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously over 10 min. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. Microdialysis is a catheter-based pharmacokinetic tool, that allows dynamic sampling of unbound and pharmacologic active fraction of drugs e.g., cefuroxime. The primary endpoint was the time with cefuroxime above the clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL as this has been suggested as the best predictor of efficacy for cefuroxime. The secondary endpoint was tissue penetration (AUC. tissue. /AUC. plasma. ). Results. Mean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105–141) in plasma, 97 min (79–115) in the anterior column and 93 min (75–111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40–0.56) and posterior column 0.40 (0.33–0.48). Conclusions. Open lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime resulted in comparable T>MIC between the anterior and posterior column of the lumbar spine. Mean cefuroxime concentrations decreased below the clinical breakpoint MIC for S. aureus of 4 µg/mL after 123 min (plasma), 97 min (anterior column) and 93 min (posterior column). This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalization, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intraarticular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included débridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 µg/mL. Mean serum vancomycin peak concentration was 6 ± 2 µg/mL and the mean serum vancomycin trough concentration was 3 ± 1 µg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 µg/mL and 20,167 µg/mL and trough concentrations were 724 µg/mL and 543 µg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean followup was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83 ± 9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimizing systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

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. Results. 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). Conclusions. 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

Introduction. Cement pressurisation in the distal humerus is technically difficult due to the anatomy of the humeral intramedullary (IM) cavity. Conventional cement restrictors often migrate proximally or leak, reducing the effect of pressurisation during implantation. Theoretically with a better cement bone interdigitation, the longevity of the elbow replacement can be improved. The aim of this cadaveric study was to evaluate the usefulness of a novel technique for cementation. Method. Eight paired fresh frozen cadaveric elbows were randomly allocated to conventional cementing techniques or cementing using a paediatric foley catheter as a temporary restrictor. The traditional cementing technique consisted of canal preparation using irrigation, brushing and drying prior to cementation, with no use of a cement restrictor. The new technique involved same canal preparation but prior to cementation a size 8 foley catheter was introduced and the balloon inflated to act as a temporary cement restrictor. The humeri were cut into 10mm sections. Each slice was photographed and radiographed. This dual imaging technique was used to establish the best methodology for evaluation of cement penetration. Cement penetration was calculated as a ratio of the area of intra-medullary cavity occupied by the cement. Results. There was no significant difference between the photographic and radiographic method of measuring cement penetration. Cement penetration was significantly better in the foley catheter group (P = 0.002-0.037). The maximum penetration was observed in the most distal 2-5cm. Conclusion. The foley catheter technique consistently and significantly achieved a better cement interdigitation into the cancellous bone, without leaving a void in the cement. This study has demonstrated a new cementing technique for elbow arthroplasty, utilising a paediatric foley catheter as a temporary humeral intra-medullary plug, increasing cement pressurisation and restricting proximal cement migration. Future studies using this methodology will not require supplementation of photographs with radiographic analysis

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalisation, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intraarticular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration (avg. of 6.8 and 9,242 µg/mL). Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (minimum trough levels of 8.4 and 4.2 µg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was 3.1 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included debridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 µg/mL. Mean serum vancomycin peak concentration was 6±2 µg/mL and the mean serum vancomycin trough concentration was 3±1 µg/mL at 2 weeks postoperative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 µg/mL and 20,167 µg/mL and trough concentrations were 724 µg/mL and 543µg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean followup was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83±9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months postoperatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimising systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

Infection is one of the most devastating complications following total joint arthroplasty. Treatment is difficult, often requiring multiple surgical procedures, prolonged hospitalisation, and long-term intravenous (IV) antibiotic therapy. Failure rates are high for resistant organisms and mixed-flora infections, and antibiotic-loaded cement spacers deliver antibiotics for only a few days and can harbor resistant bacteria on the surface. We have adopted a direct-exchange method with antibiotics infused directly into the joint using Hickman catheters to achieve extremely high levels of intra-articular (IA) antibiotics for six weeks. Hickman catheters have a fibrous cuff that allows soft-tissue ingrowth and seals the surface of the tube to prevent contamination of the joint by tracking along the catheter. Two catheters are inserted to ensure that at least one will be functional for six weeks. The safety and efficacy of this protocol was evaluated in patients undergoing primary or revision TKA by measuring joint and serum levels of vancomycin following IV administration (as a prophylactic) and IA administration (as a treatment for infected TKA), and comparing the levels with each method. Therapeutic levels of vancomycin were present in the knee following IV or IA administration, but much higher levels were possible with IA administration. Vancomycin achieved therapeutic levels in the synovial fluid of the knee with IV administration, but clearance from the knee was rapid, suggesting that the synovial fluid concentration may be sub-therapeutic for hours before the next IV dose is given. In contrast, IA delivery of vancomycin resulted in peak levels that were many orders of magnitude higher, and trough levels remained therapeutic for 24 hours in both the joint space and in the serum (trough levels of 8.4 and 4.2 μg/mL, respectively). The elimination constant (half-life) of IA-administered vancomycin was determined to be 3.06 hours. This protocol was used in 18 knees (18 patients) with methicillin-resistant Staphylococcus aureus treated between January 2001 and January 2007 with one-stage revision that included debridement, uncemented revision of total knee components, and IA infusion of 500 mg vancomycin via Hickman catheter once or twice daily for 6 weeks. No IV antibiotics were used after the first 24 hours. Serum vancomycin levels were monitored to maintain levels between 3 and 10 μg/mL. Mean serum vancomycin peak concentration was 6±2 μg/mL and the mean serum vancomycin trough concentration was 3±1 μg/mL at 2 weeks post-operative. Knee synovial fluid peak and trough vancomycin levels were measured in two knees. Synovial fluid peak concentrations were 10,233 μg/mL and 20,167 μg/mL and trough concentrations were 724 μg/mL and 543μg/mL, respectively. Minimum follow-up was 27 months (range, 27–75 months). Mean follow-up was 62 months, (range, 27–96 months). At 2-year follow-up, mean Knee Society score was 83±9. No radiographic evidence of implant migration has occurred. One knee reinfected with MRSA and was reoperated at 5 months. A necrotic bone segment was found, the knee was debrided and revised, and the antibiotic infusion protocol was readministered. The knee remained free of infection at 42 months post-operatively. Directly infusing antibiotics into the infected area maintains a high local concentration level while minimising systemic toxicity. This method avoids the use of antibiotic-loaded cement and the potential for growth of antibiotic-resistant strains of bacteria. These findings support single-stage revision in cases treated with cementless revision and IA antibiotics

Rapid discharge pathways (RDP) have been implemented throughout most areas of orthopaedics. The primary goal of these pathways is to standardize the post-surgical hospital course for patients in order to decrease hospital length-of-stay (LOS). Surgical treatment of adolescent idiopathic scoliosis (AIS) remains one of the most invasive pediatric orthopaedic procedure and is routinely associated with a prolonged hospital stay. The implementation of RDPs following surgery for AIS has shown to be successful; however, all of these studies have been conducted within the United States and it has been shown previously that there exists major differences in hospital LOS and in post-operative complications between Canada and the United States. Therefore, the objective of this study was to determine if the implementation of a RDP at a single children's tertiary-referral centre in Canada could decrease hospital LOS without increasing post-operative complications. A retrospective chart review was completed for all patients who underwent posterior spinal instrumentation and fusion (PSIF) between March 1st, 2010 and February 28th, 2019, with date of implementation being March 1st, 2015. Patient pre-operative, operative, and post-operative information was collected from the charts along with the primary outcome variables: LOS, wound complication, 30-day return to the OR, 30-day emergency department admission, and 30-day hospital readmission. An interrupted time series analysis with a robust linear regression model was utilized to assess for any differences in outcomes following implementation of the RDP. Ninety days before and after the implementation of the RDP was not included in this analysis due to variances in practice that were occurring at this time. A total of 244 participants were identified, with 113 patients in the conventional pathway and 131 patients in the RDP cohort. No significant differences in pre-operative or operative characteristics existed between the groups, except for the RDP group having approximately a 50 larger pre-operative curve and the conventional pathway having on average 200mL greater intra-operative blood loss (p<0.05). Hospital LOS was found to be significantly shorter in the RDP group, with the median LOS being 5.2 [95% IQR 4.3–6.1] days in the conventional group and 3.4 [95% IQR 3.3–3.5] days in the RDP group (p<0.05). Patients in the RDP group were also found to stand 0.9 days earlier, walk 1.1 days earlier, their Foley catheter was discontinued 0.5 days earlier and their personal controlled analgesia was discontinued 12 hours sooner (p<0.05). There were no differences in post-operative complications between the two groups (p>0.05). This study demonstrates that implementing a RDP following PSIF for AIS can successfully decrease hospital LOS without increasing post-operative complications in a single payer universal healthcare system. The associated decrease in LOS could correlate with decreasing costs for both the healthcare system and for the patient's family