Aims. In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from ‘high-risk’ patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. Methods. TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA. Results. Between July 2016 and July 2018, 552 patients were randomized to either Group 1 (n = 241), Group 2 (n = 243), or Group 3 (n = 68), and 551 were included in the final analysis. The blood loss did differ significantly between the two intervention groups (733.5 ml (SD 384.0) for Group 1 and 859.2 ml (SD 363.6 ml) for Group 2; mean difference -125.8 ml (95% confidence interval -194.0 to -57.5; p < 0.001). No differences in mortality or thromboembolic events were observed in any group. Conclusion. These data support the hypothesis that in TKA, a TXA regime consisting of IV 1 g perioperatively and four oral 1 g doses over 24 hours postoperatively significantly reduces blood loss beyond that achieved with a single IV 1 g perioperative dose alone. TXA appears safe in patients with history of thromboembolic, cardiovascular, and cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(10):1595–1603

Aims. Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up. Methods. A retrospective review of 1,060 patients who underwent TKA between May 2016 to July 2020 was performed. There were 572 patients in the IV group and 488 in the IO group, with minimal 30 days of follow-up. Patients were followed up at regularly scheduled intervals (two, six, and 12 weeks). No differences between groups for age, sex, BMI, or baseline comorbidities existed. The IV group received an IV dose of 15 mg/kg vancomycin given over an hour preceding skin incision. The IO group received a 500 mg dose of vancomycin mixed in 150 ml of normal saline, injected into proximal tibia after tourniquet inflation, before skin incision. All patients received an additional dose of first generation cephalosporin. Evaluation included preoperative and postoperative serum creatinine values, tourniquet time, and adverse reactions attributable to vancomycin. Results. Incidence of PJI with minimum 90-day follow-up was 1.4% (eight knees) in the IV group and 0.22% (one knee) in IO group (p = 0.047). This preliminary report demonstrated an reduction in the incidence of infection in TKA using IO vancomycin combined with a first-generation cephalosporin. While the study suffers from limitations of a retrospective, multi-surgeon investigation, early findings are encouraging. Conclusion. IO delivery of vancomycin after tourniquet inflation is a safe and effective alternative to IV administration, eliminating the logistical challenges of timely dosing. Cite this article: Bone Joint J 2021;103-B(6 Supple A):13–17

Aims. Blood transfusion and postoperative anaemia are complications of total knee arthroplasty (TKA) that are associated with substantial healthcare costs, morbidity, and mortality. There are few data from large datasets on the risk factors for these complications. Methods. We retrospectively reviewed the records of TKA patients from a single tertiary care institution from February 2016 to December 2020. There were a total of 14,901 patients in this cohort with a mean age of 67.9 years (SD 9.2), and 5,575 patients (37.4%) were male. Outcomes included perioperative blood transfusion and postoperative anaemia, defined a priori as haemoglobin level < 10 g/dl measured on the first day postoperatively. In order to establish a preoperative haemoglobin cutoff, we investigated a preoperative haemoglobin level that would limit transfusion likelihood to ≤ 1% (13 g/dl) and postoperative anaemia likelihood to 4.1%. Risk factors were assessed through multivariable Poisson regression modelling with robust error variance. Results. In multivariable analyses, each gram of tranexamic acid reduced transfusion likelihood by 39% (adjusted risk ratio (ARR) 0.61 (95% confidence interval (CI) 0.47 to 0.78)). Risk factors associated with an increased risk of transfusion included operating time (ARR 2.07 (95% CI 1.54 to 2.77)) and drain use (ARR 1.73 (95% CI 1.34 to 2.24)). Conclusion. In this study, we found that increased tranexamic acid dosing, decreased operating time, and decreased drain use may reduce transfusions following TKA. We also established a single preoperative haemoglobin cutoff of 13 g/dl that could help minimize transfusions and reduce postoperative complete blood counts. Cite this article: Bone Joint J 2023;105-B(10):1086–1093

Aims. The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and Methods. In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results. Groups C (661.1 ml, . sd. 262.4) and D (597.7 ml, . sd. 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively). Groups C (2.22 ml, . sd. 0.91) and D (2.04 ml, . sd. 0.95) had a lower reduction in the level of haemoglobin than groups A and B. However, there were no differences between groups C and D in relation to the three parameters. Conclusion. The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025–32

Aims. Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. Patients and Methods. From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. Results. In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. Conclusion. Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10–16

Aims. The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods. This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results. The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion. Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190

Aims. The aims of this study were to compare the efficacy and safety of intra-articular and intravenous (IV) tranexamic acid (TXA) in controlling perioperative blood loss in total knee arthroplasty (TKA) using a randomized, double-blinded equivalence trial. Patients and Methods. A total of 182 patients aged between 45 and 75 years undergoing unilateral TKA at a tertiary centre were randomized to receive TXA, either 1.5 g intra-articularly after closure of the wound (n = 91) or two doses of 10 mg/kg IV (n = 91). The primary outcome measure was the reduction in the level of haemoglobin (Hb) in the blood on the fifth postoperative day. Secondary outcome measures were the total, visible, and hidden blood losses (TBL, VBL, HBL). We assumed equivalence of the primary outcome in both routes with a margin of ± 0.35gm/dl. Block randomization using computer-generated random numbers was used. The patients and the assessor of outcome were blinded. Results. All patients completed the study. The mean difference in the reduction of the level of Hb between the two groups was -0.0055 gm/dl, with two-sided 95% confidence interval (CI) being -0.29 to 0.27, well within the predefined equivalence margin of ± 0.35gm/dl. The groups were comparable with regard to TBL, VBL, HBL, and complications. No patient needed a blood transfusion. Conclusion. A single intra-articular dose and two IV doses of TXA give equivalent efficacy and safety in the management of blood loss at TKA. Cite this article: Bone Joint J 2018;100-B:152–60

Aims. Enhanced perioperative protocols have significantly improved patient recovery following primary total knee arthroplasty (TKA). Little has been investigated the effectiveness of these protocols for revision TKA (RTKA). We report on a matched group of aseptic revision and primary TKA patients treated with an identical pain and rehabilitation programmes. Methods. Overall, 40 aseptic full-component RTKA patients were matched (surgical date, age, sex, and body mass index (BMI)) to a group of primary cemented TKA patients. All RTKAs had new uncemented stemmed femoral and tibial components with metaphyseal sleeves. Both groups were treated with an identical postoperative pain protocol. Patients were followed for at least two years. Knee Society Scores (KSS) at six weeks and at final follow-up were recorded for both groups. Results. There was no difference in mean length of stay between the primary TKA (1.2 days (0.83 to 2.08)) and RTKA patients (1.4 days (0.91 to 2.08). Mean oral morphine milligram (mg) equivalent dosing (MED) during the hospitalization was 42 mg/day for the primary TKA and 38 mg/day for the RTKA groups. There were two readmissions: gastrointestinal disturbance (RTKA) and urinary retention (primary TKA). There no were reoperations, wound problems, thromboembolic events or manipulations in either group. Mean overall KSS for the RTKA group was 87.3 (45 to 99) at six-week follow-up and 89.1 (52 to 100) at final follow-up (mean 3.9 years, (3.9 to 9.0)). Mean overall KSS for the primary group was 89.9 (71 to 100) at six-week follow-up and 93.42 (73 to 100) at final follow-up (mean 3.5 years (2.5 to 9.2)). Conclusion. An identical pain and rehabilitation protocol used for primary TKA patients can enable certain full-component aseptic RTKA patients to have a similar early functional outcome. Cite this article: Bone Joint J 2020;102-B(6 Supple A):96–100

Aims

The tibial component of total knee arthroplasty can either be an all-polyethylene (AP) implant or a metal-backed (MB) implant. This study aims to compare the five-year functional outcomes of AP tibial components to MB components in patients aged over 70 years. Secondary aims are to compare quality of life, implant survivorship, and cost-effectiveness.

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This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection.

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The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

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Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear.

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The primary aim was to assess whether robotic total knee arthroplasty (rTKA) had a greater early knee-specific outcome when compared to manual TKA (mTKA). Secondary aims were to assess whether rTKA was associated with improved expectation fulfilment, health-related quality of life (HRQoL), and patient satisfaction when compared to mTKA.

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Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

Aim. Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Materials and Methods. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 10. 6. MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Results. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. Conclusion. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824–831

Aims

Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP.

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Single-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone.

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Thresholds of acceptable early migration of the components in total knee arthroplasty (TKA) have traditionally ignored the effects of patient and implant factors that may influence migration. The aim of this study was to determine which of these factors are associated with overall longitudinal migration of well-fixed tibial components following TKA.