Adequate visual clarity is paramount to performing arthroscopic shoulder surgery safely, efficiently, and effectively. The addition of epinephrine in irrigation fluid, and the intravenous or local administration of tranexamic acid (TXA) have independently been reported to decrease bleeding thereby improving the surgeon's visualization during arthroscopic shoulder procedures. No study has compared the effect of systemic administered TXA, epinephrine added in the irrigation fluid or the combination of both TXA and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. The purpose of this study is to determine if intravenous TXA is a safe alternative to epinephrine delivered by a pressure-controlled pump in improving arthroscopic shoulder visualization during arthroscopic procedures and whether using both TXA and epinephrine together has an additive effect in improving visualization. The design of the study was a double-blinded, randomized controlled trial with four 1:1:1:1 parallel groups conducted at one center. Patients aged ≥18 years undergoing arthroscopic shoulder procedures including rotator cuff repair, arthroscopic biceps tenotomy/tenodesis, distal clavicle excision, subacromial decompression and labral repair by five fellowship-trained upper extremity surgeons were randomized into one of four arms: Pressure pump-controlled regular saline irrigation fluid (control), epinephrine (1ml of 1:1000) mixed in irrigation fluid (EPI), 1g intravenous TXA (TXA), and epinephrine and TXA (EPI/TXA). Visualization was rated on a 4-point Likert scale every 15 minutes with 0 indicating ‘poor’ quality and 3 indicating ‘excellent’ quality. The primary outcome measure was the unweighted mean of these ratings. Secondary outcomes included mean arterial blood pressure (MAP), surgery duration, surgery complexity, and adverse events within the first postoperative week. One hundred and twenty-eight participants with a mean age (± SD) of 56 (± 11) years were randomized. Mean visualization quality for the control, TXA, EPI, and EPI/TXA groups were 2.1 (±0.40), 2.1 (±0.52), 2.6 (±0.37), 2.6 (±0.35), respectively. In a regression model with visual quality as the dependent variable, the presence/absence of EPI was the most significant predictor of visualization quality (R=0.525; p < 0 .001). TXA presence/absence had no effect, and there was no interaction between TXA and EPI. The addition of MAP and surgery duration strengthened the model (R=0.529; p < 0 .001). Increased MAP and surgery duration were both associated with decreased visualization quality. When surgery duration was controlled, surgery complexity was not a significant predictor of visualization quality. No adverse events were recorded in any of the groups. Intravenous administration of TXA is not an effective alternative to epinephrine in the irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries although its application is safe. There is no additional improvement in visualization when TXA is used in combination with epinephrine beyond the effect of epinephrine alone

Adequate visual clarity is paramount to performing arthroscopic shoulder surgery safely, efficiently, and effectively. The addition of epinephrine in irrigation fluid, and the intravenous or local administration of tranexamic acid (TXA) have independently been reported to decrease bleeding thereby improving the surgeon's visualization during arthroscopic shoulder procedures. No study has compared the effect of systemic administered TXA, epinephrine added in the irrigation fluid or the combination of both TXA and epinephrine on visual clarity during shoulder arthroscopy with a placebo group. The purpose of this study is to determine if intravenous TXA is a safe alternative to epinephrine delivered by a pressure-controlled pump in improving arthroscopic shoulder visualization during arthroscopic procedures and whether using both TXA and epinephrine together has an additive effect in improving visualization. The design of the study was a double-blinded, randomized controlled trial with four 1:1:1:1 parallel groups conducted at one center. Patients aged ≥18 years undergoing arthroscopic shoulder procedures including rotator cuff repair, arthroscopic biceps tenotomy/tenodesis, distal clavicle excision, subacromial decompression and labral repair by five fellowship-trained upper extremity surgeons were randomized into one of four arms: Pressure pump-controlled regular saline irrigation fluid (control), epinephrine (1ml of 1:1000) mixed in irrigation fluid (EPI), 1g intravenous TXA (TXA), and epinephrine and TXA (EPI/TXA). Visualization was rated on a 4-point Likert scale every 15 minutes with 0 indicating ‘poor’ quality and 3 indicating ‘excellent’ quality. The primary outcome measure was the unweighted mean of these ratings. Secondary outcomes included mean arterial blood pressure (MAP), surgery duration, surgery complexity, and adverse events within the first postoperative week. One hundred and twenty-eight participants with a mean age (± SD) of 56 (± 11) years were randomized. Mean visualization quality for the control, TXA, EPI, and EPI/TXA groups were 2.1 (±0.40), 2.1 (±0.52), 2.6 (±0.37), 2.6 (±0.35), respectively. In a regression model with visual quality as the dependent variable, the presence/absence of EPI was the most significant predictor of visualization quality (R=0.525; p < 0 .001). TXA presence/absence had no effect, and there was no interaction between TXA and EPI. The addition of MAP and surgery duration strengthened the model (R=0.529; p < 0 .001). Increased MAP and surgery duration were both associated with decreased visualization quality. When surgery duration was controlled, surgery complexity was not a significant predictor of visualization quality. No adverse events were recorded in any of the groups. Intravenous administration of TXA is not an effective alternative to epinephrine in the irrigation fluid to improve visualization during routine arthroscopic shoulder surgeries although its application is safe. There is no additional improvement in visualization when TXA is used in combination with epinephrine beyond the effect of epinephrine alone

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). Results. Intravenous administration resulted in longer fT>MIC (0.5 μg/mL) compared to oral administration, except for cortical bone. In Group IV all pigs reached a concentration of 0.5 μg/mL in all compartments. The mean fT>MIC (0.5 μg/mL) was 149 min in subcutaneous tissue and 61–106 min in bone tissue. In Group PO 0/8 pigs reached a concentration of 0.5 μg/mL in all compartments. For the high MIC target (2.0 μg/mL), fT>MIC was close to 0 min in both groups across compartments. Conclusions. Although intravenous administration of flucloxacillin 1g provided higher fT>MIC for the low MIC target compared to oral administration, concentrations were surprisingly low, particularly for bone tissue. Achievement of sufficient bone and soft tissue flucloxacillin concentrations may require a dose increase or continuous administration. Acknowledgement. The study was supported by the following grants: Sofus Carl Emil Friis Foundation, Aase & Ejnar Danielsens Foundation, the Augustinus Foundation, Direkt⊘r Emil Hertz og hustru Inger Hertz Foundation, and the Novo Nordisk Foundation

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

To compare the efficacy of intra-articular and intravenous modes of administration of tranexamic acid in primary Total Knee Arthroplasty in terms of blood loss and fall in haemoglobin level. This randomized controlled trial was conducted from 12th May 2017 to 11th May 2017. Seventy eight patients were included in the study. Patients were randomly divided into group A and B. Group A patients undergoing unilateral primary total knee replacement (TKR) were given intravenous tranexamic acid (TXA) while group B were infiltrated with intra-articular TXA. Volume of drain output, fall in haemoglobin (Hb) level and need for blood transfusion were measured immediately after surgery and at 12 and 24 hours post operatively in both groups. The study included 35 (44.87%) male and 43 (55.13%) female patients. Mean age of patients was 61±6.59 years. The mean drain output calculated immediately after surgery in group A was 45.38±20.75 mL compared with 47.95±23.86 mL in group B (p=0.73). 24 hours post operatively, mean drain output was 263.21±38.50 mL in intravenous group versus 243.59±70.73 mL in intra-articular group (p=0.46). Regarding fall in Hb level, both groups showed no significant difference (p>0.05). 12.82% (n=5) patients in group A compared to 10.26% (n=4) patients required blood transfusion post operatively (p=0.72). Intra-articular and intravenous TXA are equally effective in patients undergoing primary total knee arthroplasty in reducing post operative blood loss. For any reader queries, please contact . drjunaidrmc@gmail.com

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

Tranexamic acid (TEA), an antifibrinolytic agent, is routinely used for reduction of blood loss in total hip arthroplasty (THA). However, use of intravenous (IV) TEA has been questioned due to safety concerns and a lack of biochemical data in the arthroplasty literature. Tranexamic acid given topically as a periarticular solution is a promising alternative route of administration. The purpose of this study is to identify differences in systemic absorption for intravenous and topical TEA administered during primary THA. In a blinded randomised controlled trial of patients undergoing primary cementless total hip arthroplasty, 29 participants received a weight-based bolus infusion of intravenous TEA (20 mg/kg) 10 minutes prior to skin incision. Conversely, 15 participants received a 1.5 g bolus dose of TEA administered topically into the periarticular region of the operative hip at the time of arthrotomy closure. A blood sample was drawn one hour post-administration for measurement of serum TEA concentration (µg/mL) by tandem mass spectrometry. In addition to comparing mean concentration levels for both treatment arms, each sample concentration was referenced to a pre-determined TEA concentration threshold of 10 µg/mL, a value known to represent 80% tissue plasminogen activator (tPA) inhibition in vivo. Those participants receiving topical TEA had four-fold lower TEA levels at one hour postoperatively (mean 12.44 ± 17.59 versus 52.54 ± 23.94 µg/mL, p<0.05). These results demonstrate significantly lower circulating TEA at one hour after topical administration. Intravenous TEA must travel through the intravascular compartment in order to reach the operative hip. Topical administration of TEA targets bleeding tissues within the surgical field without necessitating parenteral administration. This results in less inhibition of tPA away from the operative site, potentially decreasing the risk of developing a pro-thrombotic state postoperatively. Correlating these results with outcomes from clinical efficacy trials comparing intravenous and topical TEA use in THA will further clarify optimal dosing strategies

Introduction. In recent years, many studies demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopaedic related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods. We conducted a retrospective observational multicenter study in patients diagnosed with an early postoperative PJI (i.e less than 3 months after the index arthroplasty) treated with debridement, antibiotics and implant retention (DAIR). Patients from Europe and the USA were included. These two cohorts served as a quasi-randomised trial since an early oral antibiotic switch is routine practice in Europe versus a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for: i) a second DAIR, ii) implant removal, iii) suppressive antibiotic treatment or iv) infection related death. Results. A total of 668 patients were included. 277 received IV antibiotics for <14 days, 232 were given IV antibiotics between 14 - 27 days and 159 received IV antibiotics for >27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4% and 42.1%, respectively (P 0.80), and mainly comprised the need for a second DAIR. The results did not change when analyzing patients with or without obesity, the causative microorganism or the type of oral antibiotics. Conclusion. In early postoperative PJIs, a longer duration of IV antibiotic treatment is not associated with a lower failure rate of a DAIR procedure

Aim. Prosthetic joint infection (PJI) concerns up to 20% of all prosthesis revision procedures. The IDSA recommends at least 2 weeks of intravenous antimicrobial therapy while most of the appropriate antibiotics in these settings have very high oral bioavailability (e.g., rifampicin, cotrimoxazole, fluoroquinolone, clindamycin, fusidic acid, linezolid and doxycycline). Method. AVAPOM is a monocentric retrospective non-inferiority study which included patients who received at least one of the highly bioavailable antibiotics listed above as a documented treatment (i.e., following the intravenous empirical post-operative antibiotic treatment) for PJIs in order to compare the remission rate of infection and the length of hospital stay (LOS). Patients were split between intravenous group (IV, from 1st January 2013 to 31st December 2014) and complete oral group (PO; since 1st January 2015) and were compared on both the PJI outcome regarding the last news available and the length of stay (LOS). Results. Out of a total of 216 patients, our intermediary analysis included 141 patients, with 73 receiving IV treatment (IV) and 68 oral treatment (PO). Remission was recorded in 21.9% IV patients and in 25.0% PO patients after a mean follow-up of 410.4 days ± 36.3 days (p=0.26). The global mortality reached 6.41% in IV group versus 1.25% in PO group (p=0.15). The medium LOS was 16.9 and 12.5 days for respectively IV and PO groups (p=0.0001). Conclusions. Our preliminary results suggest that complete oral and intravenous documented antibiotic treatment for patients with PJIs are comparable with regards to the patients' outcome but oral treatment is associated with a significant reduction of LOS

Purpose. This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in hemoglobin levels. Materials and Methods. Studies were included in this meta-analysis if they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in hemoglobin before and after surgery in primary TKA with TXA administered through both the intravenous (IV) and topical routes.[Fig. 1]. Results. Ten studies were included in this meta-analysis.[Fig. 2] The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95% CI: 0.63 to 2.81; P=0.45) [Fig. 3] and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95% CI: 0.41 to 1.77; P=0.66) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95% CI: −50.74 to 185.66 ml; P=0.44),[Fig. 4] 21.5 mL greater estimated blood loss (95% CI: −98.05 to 55.12 ml; P=0.32), and 51.4 mL greater total blood loss (95% CI: −208.16 to 105.31 ml; P=0.52) [Fig. 5]in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in hemoglobin levels (0.02 g/dl, 95% CI: −0.36 to 0.39 g/dl; P=0.94). Conclusion. In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in hemoglobin levels between the intravenous and topical administration of TXA. For figures/tables, please contact authors directly.

Objectives. Tranexamic acid (TXA), an inhibitor of fibrinolysis blocking the lysine-binding site of plasminogen to fibrin, has been reported to reduce intraoperative and postoperative blood loss in patients undergoing primary total hip arthroplasty (PTHA) both with and without cement. Both intravenous (IV) and topical (TOP) administration of TXA can effectively reduce blood loss in THA without increasing risk of deep venous thrombosis (DVT). However, there have been few reports investigating the combination of intravenous and topical administration of TXA in bilateral cementless PTHA. We investigated the effects of combined intravenous and topical administration of TXA on postoperative blood loss, drainage volume, and perioperative complications in patients with bilateral simultaneous cementless PTHA for hip osteoarthritis. Patients and methods. We retrospectively reviewed the demographic and clinical data of 41 patients who underwent bilateral simultaneous cementless PTHA for hip osteoarthritis from May 2015 to January 2017, of which there were 29 male (70.7%) and 12 female (29.3%) patients. Patients in IV group (n= 11) received only TXA (15 mg/kg) 10 min prior to the incision of each side; and patients in IV + TOP group (n=13) received i.v. TXA (15 mg/kg) combined with topical adiministration (1.0 g) of TXA during the each THA procedure; patients in control group (n=17) received the same dosage of normal saline both i.v. and topically. Outcome measures were total blood loss, hemoglobin, hematocrit value (HCT) changes preoperatively, and on the 1st, 3rd postoperative day, the amount of drainage, and perioperative complications. Results. On the 1st, 3rd postoperative day, patients in group IV and group IV + TOP had significantly higher haematological parameters (haemoglobin, hematocrit value (HCT)) than patients in control group (P < 0.05 (group IV vs control group), P < 0.01 (group IV + TOP vs control group), respectively), while no significant differences found between patients in group IV and group IV + TOP (P > 0.05). The postoperative drainage volume of patients in group IV and group IV + TOP were significantly less than those in control group (P < 0.01, P < 0.01, respectively), while no significant differences found between those in group IV and group IV + TOP (P > 0.05). No significant differences were found in the perioperative complications (DVT or PE) among all three groups. Conclusion. The combined administration of intravenous and topical TXA resulted in a significantly reduction in postoperative blood loss, compared with placebo group. No adverse perioperative complications were observed. This study supports the combined intravenous and topical administration of TXA in bilateral cementless PTHA

Aims. Vancomycin may be an important drug for intravenous perioperative antimicrobial prophylaxis in spine surgery. We assessed single-dose vancomycin intervertebral disc, vertebral cancellous bone, and subcutaneous adipose tissue concentrations using microdialysis in a pig model. Methods. 8 female pigs received 1,000 mg of vancomycin intravenously as a single dose over 100 minutes. Microdialysis probes were placed in the C3-C4 intervertebral disc, C3 vertebral cancellous bone, and subcutaneous adipose tissue, and vancomycin concentrations were obtained over 8 hours. Venous blood samples were obtained as reference. Results. Ranging from 0.24 to 0.60, vancomycin tissue penetration, expressed as the ratio of tissue to plasma area under the concentration-time curve from 0 to the last measured value, was incomplete for all compartments. The lowest penetration was found in the intervertebral disc. The time to a mean clinically relevant minimal inhibitory concentration (MIC) of 4 μg/mL were 3, 17, 25, and 156 min for plasma, subcutaneous adipose tissue, vertebral cancellous bone and the intervertebral disc, respectively. In contrast to the other compartments, a mean MIC of 8 μg/mL was not reached in the intervertebral disc. An approximately 3-time longer elimination rate was observed in the intervertebral disc in comparison to all the other compartments (p < 0.001), and the time to peak drug concentration was higher for all tissues compared with plasma. Conclusions. Preoperative administration of 1,000 mg of vancomycin may provide adequate vancomycin tissue concentrations with a considerable delay, though tissue penetration was incomplete. However, in order also to achieve adequate intervertebral disc concentrations in all individuals and accommodating a potentially higher MIC target, supplemental application of vancomycin may be necessary

Introduction. Bilateral total knee arthroplasty (TKA) results in substantial perioperative blood loss with increased morbidity. Tranexamic acid (TXA) administration in either intravenous or topical form has been found to be effective in reducing perioperative blood loss. The objective of the present study was to compare the efficacy of topical versus intravenous TXA in reducing perioperative blood loss. Methods. Prospective, randomized, double-blinded clinical trial was carried out on 70 patients undergoing bilateral TKA, who were divided into two groups. Group I received equivalent dose of TXA intravenously 30 minutes prior to deflation of tourniquet of first knee and another dose repeated after 2 hours. Group 2 received topical TXA in the dose of 15mg/kg dissolved in100 ml of normal saline which was applied into the joint for 10 minutes at the end of implant insertion. Outcome measures were total blood loss as (calculated from the difference between preoperative and postoperative day3 haemoglobin (Hb) or Hb prior to transfusion), total drain output and amount of blood transfusion. Results. Perioperative blood loss in group 2 (561.42 ± 248.99) was reduced significantly as compared to group 1 (1037.04 ±506.650) with a p-value of <0.001. The postoperative Hb in group 2 (10.30± 1.11) was also significantly higher as compared to group 1(9.66±1.47) with a p-value of <0.001. Total drain output in group 2 (269.14± 120.98) was significantly reduced as compared to group 1(574.14± 269.03) with a p-value of <0.001. There were no reports of deep vein thrombosis or pulmonary embolism in either group. Conclusion. Topical application of tranexamic acid significantly decreases the blood loss in bilateral total knee arthroplasty as compared to intravenous administration, with a mean reduction by about 45% with respect to inravenous group

The current standard recommendation for antibiotic therapy in the management of chronic osteomyelitis is intravenous treatment for six weeks. We have compared this regime with short-term intravenous therapy followed by oral dosage. A total of 93 patients, with chronic osteomyelitis, underwent single-stage, aggressive surgical debridement and appropriate soft-tissue coverage. Culture-specific intravenous antibiotics were given for five to seven days, followed by oral therapy for six weeks. During surgery, the scar, including the sinus track, was excised en bloc. We used a high-speed, saline-cooled burr to remove necrotic bone, and osseous laser Doppler flowmetry to ensure that the remaining bone was viable. Infected nonunions (Cierny stage-IV osteomyelitis) were stabilised by internal fixation. In 38 patients management of dead space required antibiotic-impregnated polymethylmethacrylate beads, which were exchanged for an autogenous bone graft at six weeks. Free-tissue transfer often facilitated soft-tissue coverage. These 93 patients were compared with 22 consecutive patients treated previously who had the same surgical management, but received culture-specific intravenous antibiotics for six weeks. Of the 93 patients, 80 healed without further intervention. Of the 31 Cierny-IV lesions, 27 healed without another operation, and four fractures required additional bone grafts. No more wound drainage was needed. Treatment was successful in 91% of patients, regardless of the organism involved. There was no difference in outcome in terms of these variables when the series were compared. We conclude that the long-term administration of intravenous antibiotics is not necessary to achieve a high rate of clinical resolution of wound drainage for adult patients with chronic osteomyelitis

Aim. We evaluated the efficacy and safety of treatment regimens in a pathogen and surgery specific mode according to a standardized algorithm for the treatment of periprosthetic joint infection (PJI) based on combinations with 15g/d intravenous fosfomycin followed by oral antibiotics for totally 12 weeks. Method. Consecutive patients with PJI caused by at least one of the following isolates were prospectively included: staphylococci (MIC ≤32 mg/l), streptococci (MIC ≤128 mg/l), enterococci (MIC ≤128 mg/l), Enterobacteriaceae (MIC ≤32 mg/l) and Pseudomonas spp. (MIC ≤128 mg/l). PJI was defined by the proposed European Bone and Joint Infection Society (EBJIS) criteria. Follow up with clinical (joint function and quality of life scores), laboratory and radiological evaluation at 3, 12 and 24 months after last surgery is performed. Infection outcome was assessed as the proportion of infection-free patients. The probability of infection-free survival was estimated using the Kaplan-Meier survival method. Results. 50 patients were screened for eligibility, of which 2 were excluded due to intolerance or allergy to fosfomycin, 1 due to isolation of fosfomycin resistant pathogen and 2 patients died due to unrelated cause to infection. The remaining 45 patients were included. Due to persistence of infection, 3 patients underwent prosthesis explantation after initial debridement and retention, 1 patient underwent debridement of Girdlestone-situation; all 4 infections were caused by S. aureus. At 2 patients debridement of hematoma after Girdlestone approach was performed. 41 patients were infection-free (91%) after a median follow-up of 6 month (range, 1 – 14 months). Nausea (n=14) and hypokalemia (n=13) were the most frequent adverse events and resolved after fosfomycin discontinuation; 5 patients had diarrhea and vomiting was observed in 2 patients. Isolated pathogens were staphylococci (n=30), streptococci (n=3), enterococci (n=5) and gram-negative rods (n=2). Cultures were negative in 9 patients and polymicrobial in 2 patients. The infection occurred postoperatively in 31 patients (69%) and hematogenously in 14 (31%). Two-stage exchange was performed in 27 (60%), debridement with retention in 13 (29%) and one-stage exchange in 5 patients (11%). Conclusions. The applied PJI treatment algorithm including intravenous fosfomycin in the initial postoperative period was associated with infection-free outcome of 91% after a median follow-up of 6 month. The Kaplan-Meier survival method showed the probability of infection-free survival of 88.5% after 1 year. Adverse events occurred in 21 patients (46%) mostly nausea and hypokalemia were reported. Adverse events were mild and resolved completely

BACKGROUND. Optimal perioperative fluid management has not been established in patients undergoing orthopaedic surgical procedures. Our purpose was to investigate the effects of perioperative fluid management on patients experiencing TKA. METHODS. One hundred thirty patients who met inclusion criteria undergoing primary unilateral TKA were prospectively randomized into traditional (TFG) vs. oral (OFG) perioperative fluid management groups. The TFG had a predetermined amount of intravenous fluids (IVF) administered in the perioperative period. The OFG began drinking a minimum of three, 20-ounces servings of clear fluids daily for three days prior to surgery. This cohort also drank 10-ounces of clear fluids 4 hours prior to surgery. Perioperative IVF were discontinued when the patient began oral intake or when the total amount of IVF reached 500mL. Outcome measures included: body-weight (BW) fluctuations, knee motion, leg girth, bioelectrical impendence, quadriceps activation, functional outcomes testing, KOOS JR, VR-12, laboratory values, vital signs, patient satisfaction, pain scores, and adverse events. RESULTS. The TFG had increased BW the evening of surgery (7.0±4.3 vs. 3.0±3.9, p=0.000), post-operative day (POD) #1 (9.1±4.3 vs. 4.7±3.9, p=0.000), and POD #2 (6.2±5.0 vs. 4.4±4.0, p=0.032). Bioelectrical impedance showed less limb edema in the OFG (4.2±29.7 vs. 17.8±30.3, p=0.000) on POD#1. Urine specific gravity differences were seen preoperatively between groups (OFG, more hydrated, p=0.002). Systolic blood pressure change from baseline was greater in the OFG upon arrival to the floor (19.4±13.5 vs. 10.6±12.8, p=0.000) and 8 (23.4±13.3 vs. 17.0±12.9, p=0.006) and 16 (25.8±13.8 vs. 25.8±13.8, p=0.046) hours after floor arrival. The TFG had more UOP on POD#1 (3369mL±1343mL vs. 2435mL±1151mL). CONCLUSIONS. Oral fluid intake with IVF restriction in the perioperative period after TKA may offer short-term benefits with swelling and BW fluctuations. The authors continue to limit perioperative IVFs and encourage patient initiated fluid intake

Aim. Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting. Method. This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%. Results. Of 1054 participants randomised (527 to each arm) endpoint data were available for 1015 (96.30%). Definitive treatment failure was identified in 141/1015 (13.89%) participants, 74/506 (14.62%) of those randomised to IV therapy and 67/509 (13.16%) of those randomised to oral therapy. In the intention to treat analysis, the imputed risk difference (PO-IV) for definitive treatment failure was −1.38% (90% CI: −4.94, 2.19), thus meeting the non-inferiority criterion (i.e. the upper limit of 95%CI being <7.5%). A complete cases analysis, a per-protocol analysis and sensitivity analyses for missing data confirmed this result. With the exception of intravenous catheter complications, there was no significant difference between the two arms in the incidence of serious adverse events (SAEs). Health economic analysis suggests that the non-surgical treatment costs over one year for patients randomised to oral therapy were approximately £2,700 less than those of IV therapy. Conclusions. Oral antibiotic therapy is non-inferior to IV therapy when used during the first six weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within one year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Funding. The OVIVA study was funded by the National Institute for Health Research Health Technology Assessment programme (Project number 11/36/29)

Aim. Open fractures still have a high risk for fracture-related Infection (FRI). The optimal duration of perioperative antibiotic prophylaxis (PAP) for open fractures remains controversial due to heterogeneous guidelines and highly variable prophylactic regimens in clinical practice. In order to provide further evidence with which to support the selection of antibiotic duration for open fracture care, we performed a preclinical evaluation in a contaminated rabbit fracture model. Method. A complete humeral osteotomy in 18 rabbits was fixed with a 7-hole-LCP and inoculated with Staphylococcus aureus (2×106 colony forming units, CFU per inoculum). This inoculum was previously shown to result in a 100% infection rate in the absence of any antibiotic prophylaxis. Cefuroxime was administered intravenously in a weight adjusted dosage equivalent to human medicine (18.75 mg/kg) as a single shot only, for 24 hours (every 8 hours) and for 72 hours (every 8 hours) in separate groups of rabbits (n=6 per group). Infection rate per group was assessed after two weeks by quantitative bacteriological evaluation of soft tissue, bone and implants. Blood samples were taken from rabbits preoperatively and on days 3, 7 and 14 after surgery to measure white blood cell count (WBC) and C-reactive protein (CRP) levels. Results. Duration of PAP had a significant impact on the success of antibiotic prophylaxis. The single shot regimen completely failed to prevent infection. All samples (soft tissue, implant and bone) from this group displayed high numbers of bacteria. Additionally, abscesses were present in two of six rabbits. The 24-hour regimen showed a reduced infection rate (1 out of 6 rabbits infected), but only the 72-hour course was able to prevent FRI in all animals in our model. After an initial postoperative peak on day three, CRP levels then decreased to baseline (approx. 30 µg/ml) in the 24h-group and 72h-group, but remained significantly higher in the single shot group at day 7 and 14 (p<0.05). Conclusions. When contamination with high bacterial loads is likely (e.g. in an open fracture situation), a 72-hour course of intravenous cefuroxime appears to be superior in preventing FRI compared to a single shot or 24-hour antibiotic regimen. Acknowledgements. This work was funded by AOTrauma

Aim. To assess the influence of route of antibiotic administration on patient-reported outcome measures (PROMS) of individuals treated for hip and knee infections in the OVIVA multi-centre randomised controlled trial. Method. This study was designed to determine whether oral antibiotic therapy is non-inferior to intravenous (IV) therapy when given for the first six weeks of treatment for bone and joint infections. Of the 1054 participants recruited from 26 centres, 462 were treated for periprosthetic or native joint infections of the hip or knee. There were 243 participants in the IV antibiotic cohort and 219 in the oral cohort. Functional outcome was determined at baseline through to one year using the Oxford Hip/Knee Score (OHS/OKS) as joint-specific measures (0 the worse and 48 the best). An adjusted quantile regression model was used to compare functional outcome scores. Results. Of the 214 participants in the hip sub-group, 110 were randomized to IV antibiotics and 104 to oral. Of the 248 participants in the knee cohort, 133 were treated with IV antibiotics and 115 with oral. The OHS/OKS questionnaire response rate was 68%. Baseline median OHS of the hip sub-group was 14 (Interquartile range [IQR]:8–22) for the IV cohort and 12 (IQR:7–22) for the oral cohort. The one-year median OHS was 35 (IQR: 23–44) for the IV cohort and 27 (IQR:16–40) for the oral cohort with no significant difference between cohorts (p=0.181). The baseline median OKS of the knee sub-group, was 14 (IQR:8–23) for the IV cohort and 12 (IQR:8–21) for the oral cohort. The one-year median OKS was 24 (IQR: 15–35) for the IV cohort and 27 (IQR:17–38) for the oral cohort with a statistically significant difference in favour of oral therapy (p=0.036). Conclusions. At one year, there was improvement in functional outcome of patients treated with either IV or oral antibiotics in this RCT. It suggests that joint function generally improved progressively following the start of treatment irrespective of the route of antibiotic therapy. Functional outcome of patients with hip infections was similar irrespective of the route of antibiotic therapy, whereas there was statistically greater improvement in functional outcome of patients with knee infections treated with oral antibiotics. The PROMS findings of this trial support the clinical findings (i.e. infection eradication rates) and suggest that there is no advantage of using prolonged intravenous therapy as compared to oral therapy in the early treatment of infections around the hip and knee joint

In total knee arthroplasty (TKA), both intravenous (IV) and/or intra-articular (IA) administration of tranexamic acid (TXA) were showed to reduce blood loss. Moreover, research suggesting TXA decreases postoperative knee swelling, but it is unknown whether this results in improved postoperative rehabilitation outcome. Thus, the aim of this study was to evaluate whether combined IV and IA administration of TXA would associate with improved early rehabilitation outcomes. In this institutional review board approved randomized controlled trial, 179 patients scheduled for unilateral TKA were randomized to one of three regimens: (1) IA administration of 1gm TXA at end of procedure only, (2) additional preoperative IV dose of 15 mg/kg 30min before tourniquet inflation, and (3) additional postoperative dose 4hrs after preoperative dose. Primary outcomes included knee range of motion, Knee Society Score (KSS) at 6-month postoperatively, haemoglobin drop at day-2 post-operatively, and transfusion rate. Secondary outcome was venous thromboembolism (VTE) complications. Baseline characteristics were comparable between the allocation groups. Patients in regimen (3) showed statistically significant better knee extension range (6.2°, 5.9°, 2.9°, p=0.01), and KSS (88.5, 89.9, 93.0, p=0.02) at 6-month postoperatively, and lesser drop in haemoglobin at day-2 post-operatively (2.72, 2.47, 1.75 g/dL, p=0) when compared with patients in other regimens. No patients required transfusion, or complicated by VTE. The combined administration of IA and IV TXA, including both preoperative and postoperative doses, associated with statistically significantly improved early rehabilitation outcomes. The improvement may be related to higher haemoglobin level and decreased knee swelling in patients having regimen (3). For any reader queries, please contact . cpk464@yahoo.com.hk