Aims. Flucloxacillin is commonly administered intravenously for perioperative antimicrobial prophylaxis, while oral administration is typical for prophylaxis following smaller traumatic wounds. We assessed the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT > MIC) for methicillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model. Methods. A total of 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every six hours during a 24-hour period. 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 minutes (95% confidence interval (CI) 119 to 179; range 68 to 323) in subcutaneous tissue and 61 minutes (95% CI 29 to 94; range 0 to 121) to 106 minutes (95% CI 76 to 136; range 71 to 154) 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 zero minutes in both groups across compartments. Conclusion. Although intravenous administration of flucloxacillin 1 g 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. Cite this article: Bone Joint Res 2021;10(1):60–67

Aims. This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. Methods. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. Results. AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. Conclusion. The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management. Cite this article: Bone Joint Res 2024;13(10):525–534

In our department we use an enhanced recovery protocol for joint replacement of the lower limb. This incorporates the use of intravenous tranexamic acid (IVTA; 15 mg/kg) at the induction of anaesthesia. Recently there was a national shortage of IVTA for 18 weeks; during this period all patients received an oral preparation of tranexamic acid (OTA; 25 mg/kg). This retrospective study compares the safety (surgical and medical complications) and efficacy (reduction of transfusion requirements) of OTA and IVTA. During the study period a total of 2698 patients received IVTA and 302 received OTA. After adjusting for a range of patient and surgical factors, the odds ratio (OR) of receiving a blood transfusion was significantly higher with IVTA than with OTA (OR 0.48 (95% confidence interval 0.26 to 0.89), p = 0.019), whereas the safety profile was similar, based on length of stay, rate of readmission, return to theatre, deep infection, stroke, gastrointestinal bleeding, myocardial infarction, pneumonia, deep-vein thrombosis and pulmonary embolism. The financial benefit of OTA is £2.04 for a 70 kg patient; this is amplified when the cost saving associated with significantly fewer blood transfusions is considered. Although the number of patients in the study is modest, this work supports the use of OTA, and we recommend that a randomised trial be undertaken to compare the different methods of administering tranexamic acid. Cite this article: Bone Joint J 2013;95-B:1556–61

Aims. Tranexamic acid (TXA) has been shown to significantly reduce transfusion rates in primary total hip arthroplasties (THAs), but high-quality evidence is limited in the revision setting. The purpose of the current study was to compare the rate of blood transfusions and symptomatic venous thromboembolic events (VTEs) in a large cohort of revision THAs treated with or without intravenous (IV) TXA. Patients and Methods. We performed a retrospective review of 3264 revision THAs (2645 patients) between 2005 and 2014, of which 1142 procedures received IV TXA (1 g at incision and 1 g at closure). The mean age in the revision group with TXA was 65 years (28 to 95), with 579 female patients (51%). The mean age in the revision group treated without TXA was 67 years (21 to 98), with 1160 female patients (55%). Outcomes analyzed included rates of transfusion and symptomatic VTEs between procedures undertaken with and without TXA. These comparisons were performed for the overall cohort, as well as within cases subcategorized for aseptic or septic aetiologies. A propensity score was developed to minimize bias between groups and utilized age at revision THA, sex, body mass index, American Society of Anesthesiologists (ASA) score, preoperative anticoagulation, and year of surgery. Results. Tranexamic acid significantly and substantially reduced the rate of blood transfusions after revision THA overall from 54% to 26% (p < 0.001; adjusted relative risk (RR) 1.6; 95% confidence interval (CI) 1.3 to 1.9), with a significant reduction in both aseptic (49% to 18%; p < 0.001) and septic (73% to 53%; p = 0.04) revisions. The rate of VTE was minimal overall, with three events (0.3%) in the TXA group and four events (0.2%) in the non-TXA group. There were no significant differences in VTE rates based on TXA use or aetiology of revision. Conclusion. Intravenous TXA significantly reduced transfusion rates during all-cause revision THAs, including a subgroup analysis of both aseptic and septic cohorts. Adjusted risk using propensity modelling showed no statistical difference in rates of VTEs between either group. Cite this article: Bone Joint J 2019;100-B(6 Supple B):104–109

Objectives. We have increased the dose of tranexamic acid (TXA) in our enhanced total joint recovery protocol at our institution from 15 mg/kg to 30 mg/kg (maximum 2.5 g) as a single, intravenous (IV) dose. We report the clinical effect of this dosage change. Methods. We retrospectively compared two cohorts of consecutive patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery in our unit between 2008 and 2013. One group received IV TXA 15 mg/kg, maximum 1.2 g, and the other 30 mg/kg, maximum 2.5 g as a single pre-operative dose. The primary outcome for this study was the requirement for blood transfusion within 30 days of surgery. Secondary measures included length of hospital stay, critical care requirements, re-admission rate, medical complications and mortality rates. Results. A total of 1914 THA and 2537 TKA procedures were evaluated. In THA, the higher dose of TXA was associated with a significant reduction in transfusion (p = 0.02, risk ratio (RR) 0.74, 95% confidence interval (CI) 0.58 to 0.96) and rate of re-admission (p < 0.001, RR 0.50, 95% CI 0.35 to 0.71). There were reductions in the requirement for critical care (p = 0.06, RR 0.55, 95% CI 0.31 to 1.00), and in the length of stay from 4.7 to 4.3 days (p = 0.02). In TKA, transfusion requirements (p = 0.049, RR 0.64, 95% CI 0.41 to 0.99), re-admission rate (p = 0.001, RR 0.56, 95% CI 0.39 to 0.80) and critical care requirements (p < 0.003, RR 0.34, 95% CI 0.16 to 0.72) were reduced with the higher dose. Mean length of stay reduced from 4.6 days to 3.6 days (p < 0.01). There was no difference in the incidence of deep vein thrombosis, pulmonary embolism, gastrointestinal bleed, myocardial infarction, stroke or death in THA and TKA between cohorts. Conclusion. We suggest that a single pre-operative dose of TXA, 30 mg/kg, maximum 2.5g, results in a lower transfusion requirement compared with a lower dose in patients undergoing elective primary hip and knee arthroplasty. However, these findings should be interpreted in the context of the retrospective non-randomised study design. Cite this article: R. J. M. Morrison, B. Tsang, W. Fishley, I. Harper, J. C. Joseph, M. R. Reed. Dose optimisation of intravenous tranexamic acid for elective hip and knee arthroplasty: The effectiveness of a single pre-operative dose. Bone Joint Res 2017;6:499–505. DOI: 10.1302/2046-3758.68.BJR-2017-0005.R1

Aims. The purpose of the present study was to evaluate the impact of intravenous tranexamic acid on the reduction of blood loss, transfusion rate, and early post-operative clinical outcome in total shoulder arthroplasty. Patients and Methods. A randomised, placebo-controlled trial which included 54 patients undergoing unilateral primary stemless anatomical or stemmed reverse total shoulder arthroplasty was undertaken. Patients received either 100 ml saline (placebo, n = 27), or 100 ml saline together with 1000 mg of tranexamic acid (TXA, n = 27) intravenously prior to skin incision and during wound closure. Peri-operative blood loss via an intra-articular drain was recorded and total blood loss was calculated. The post-operative transfusion rate was documented. Assessment of early clinical parameters included the visual analogue scale for pain (VAS), documentation of haematoma formation and adverse events. Results. Mean peri-operative blood drainage (placebo: 170 ml versus TXA: 50 ml, p = 0.001) and calculated mean total blood loss (placebo: 1248.2 ml versus TXA: 871.0 ml, p = 0.009) were significantly lower in the TXA group. No transfusions were necessary during the study period in either group. Mean VAS for pain significantly decreased from pre-operative (VAS 7) to the early post-operative period (VAS 1.7, p < 0.001). Significant differences regarding mean post-operative pain between placebo (VAS 2.0) and TXA (VAS 1.3) were detected (p = 0.05). The occurrence of haematomas was significantly more frequent in the placebo (59.3%, n = 16) than in the TXA group (25.9%, n = 6, p = 0.027). Whereas only mild haematomas developed in the TXA group, in the placebo group a total of 22.2% (n = 6) developed either moderate or severe haematomas. No adverse events associated with administration of TXA occurred. Conclusion. Intravenous administration of TXA successfully reduced mean peri-operative blood drainage, total estimated blood loss, pain during the first post-operative days, and haematoma formation in total shoulder arthroplasty. Cite this article: Bone Joint J 2017;99-B:1073–9

Aims. Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion requirements in patients undergoing orthopaedic surgery. There remains a lack of prospective evidence for the use of TXA in patients undergoing periacetabular osteotomy (PAO). The purpose of this study was to determine if intravenous (IV) TXA is effective in reducing calculated blood loss and transfusions after PAO. Methods. This was a single-centre prospective double-blind placebo-controlled randomized trial of 81 patients aged 12 to 45 years undergoing elective PAO by a single surgeon. The intervention group (n = 40) received two doses of IV TXA of a maximum 1 g in each dose; the control group (n = 41) received two doses of 50 ml 0.9% saline IV. The primary outcome was perioperative calculated blood loss. Secondary outcomes included allogenic transfusions and six-week postoperative complications. Results. There were no differences in demographics or intraoperative variables between study groups. The TXA group demonstrated lower mean calculated blood loss (1,265 ml, (SD 321) vs 1,515 ml, (SD 394); p = 0.002) and lower frequency of allogenic transfusion (10%/n = 4 vs 37%/n = 15; p = 0.008). Regression analyses associated TXA use with significant reductions in calculated blood loss (p < 0.001) and transfusion (p = 0.007) after adjusting for age, sex, body mass index, preoperative haemoglobin, cell-saver volume, intraoperative mean arterial blood pressure, and operating time. No patients suffered venous thromboembolic complications. Conclusion. In this trial, IV TXA decreased postoperative calculated blood loss by 293 ml and reduced the frequency of allogenic transfusions by 73% (37% vs 10%) following PAO. TXA may be safe and effective for reducing blood loss in patients undergoing PAO. Cite this article: Bone Joint J 2020;102-B(9):1151–1157

Tranexamic acid (TXA), an inhibitor of fibrinolysis, reduces blood loss after total knee arthroplasty. However, its effect on minimally invasive total hip arthroplasty (THA) is not clear. We performed a prospective, randomised double-blind study to evaluate the effect of two intravenous injections of TXA on blood loss in patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of 58.1 years; 17 to 84) who underwent unilateral minimally invasive uncemented THA were randomly divided into the study group (30 patients, 20 women and ten men with a mean age of 56.5 years; 17 to 79) that received two intravenous injections 1 g of TXA pre- and post-operatively (TXA group), and a placebo group (30 patients, 15 women and 15 men with a mean age of 59.5 years; 23 to 84). We compared the peri-operative blood loss of the two groups. Actual blood loss was calculated from the maximum reduction in the level of haemoglobin. All patients were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of 441 ml (150 to 800) versus 615 ml (50 to 1580) in the placebo (p = 0.044), lower mean post-operative blood loss (285 ml (120 to 570) versus 392 ml (126 to 660) (p = 0.002), lower mean total blood loss (1070 ml (688 to 1478) versus 1337 ml (495 to 2238) (p = 0.004) and lower requirement for transfusion (p = 0.021). No patients in either group had symptoms of venous thromboembolism or wound complications. . This prospective, randomised controlled study showed that a regimen of two intravenous injections of 1 g TXA is effective for blood conservation after minimally invasive THA. Cite this article: Bone Joint J 2015;97-B:905–10

Objectives. Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. Materials and Methods. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. Results. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Conclusions. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA. Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2

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

Anthrax is extremely rare in the western world but is endemic to areas of south and central Asia. In early 2010 an outbreak was identified in heroin-injecting intravenous drug users in the United Kingdom and Europe. Afghanistan is currently the principal source of heroin which reaches the United Kingdom. When anthrax occurs, cutaneous disease accounts for over 95% of cases. At least 47 cases with 13 deaths have been confirmed so far. We present three cases presenting during this time with marked swelling, one resulting in compartment syndrome but all with an absence of the expected cutaneous appearances. We suggest that rather than cutaneous anthrax, these patients represent a new subcutaneous presentation of anthrax

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

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. Intravenous dexamethasone has been shown to reduce immediate postoperative pain after total hip arthroplasty (THA), though the effects are short-lived. We aimed to assess whether two equivalent perioperative split doses were more effective than a single preoperative dose. Methods. A total of 165 patients were randomly assigned into three groups: two perioperative saline injections (Group A, placebo), a single preoperative dose of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative doses of 10 mg dexamethasone (Group C). Patients, surgeons, and staff collecting outcome data were blinded to allocation. The primary outcome was postoperative pain level reported on a ten-point Numerical Rating Scale (NRS) at rest and during activity. The use of analgesic and antiemetic rescue, incidence of postoperative nausea and vomiting (PONV), CRP and interleukin-6 (IL-6) levels, range of motion (ROM), length of stay (LOS), patient satisfaction, and the incidence of surgical site infection (SSI) and gastrointestinal bleeding (GIB) in the three months postoperatively, were also compared. Results. The pain scores at rest were significantly lower in Groups B and C than in Group A on postoperative days 1 and 2. The dynamic pain scores and CRP and IL-6 levels were significantly lower for Groups B and C compared to Group A on postoperative days 1, 2, and 3. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, improved ROM, shorter LOS, and reported higher satisfaction than in Group A. Patients in Group C had significantly lower dynamic pain scores and IL-6 and CRP levels on postoperative days 2 and 3, and higher ROM and satisfaction on postoperative day 3 than in Group B. No SSI or GIB occurred in any group. Conclusion. Perioperative dexamethasone provides short-term advantages in reducing pain, PONV, and inflammation, and increasing range of motion in the early postoperative period after THA. A split-dose regimen was superior to a single high dose in reducing pain and inflammation, and increasing ROM, with better patient satisfaction. Level of evidence: I. Cite this article: Bone Joint J 2020;102-B(11):1497–1504

Aims. A typical pattern of blood loss associated with total hip arthroplasty (THA) is 200 ml intraoperatively and 1.3 l in the first 48 postoperative hours. Tranexamic acid (TXA) is most commonly given as a single preoperative dose only and is often withheld from patients with a history of thromboembolic disease as they are perceived to be “high-risk” with respect to postoperative venous thromboembolism (VTE). The TRanexamic ACid for 24 hours trial (TRAC-24) aimed to identify if an additional 24-hour postoperative TXA regime could further reduce blood loss beyond a once-only dose at the time of surgery, without excluding these high-risk patients. Methods. TRAC-24 was a prospective, phase IV, single centre, open label, parallel group, randomized controlled trial (RCT) involving patients undergoing primary unilateral elective THA. The primary outcome measure was the indirect calculated blood loss (IBL) at 48 hours. The patients were randomized into three groups. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional oral regime for 24 hours postoperatively, group 2 only received the intraoperative dose, and group 3 did not receive any TXA. Results. A total of 534 patients were randomized, with 233 in group 1, 235 in group 2, and 66 in group 3; 92 patients (17.2%) were considered high-risk. The mean IBL did not differ significantly between the two intervention groups (848.4 ml (SD 463.8) for group 1, and 843.7 ml (SD 478.7) for group 2; mean difference -4.7 ml (95% confidence interval -82.9 to 92.3); p = 0.916). No differences in mortality or incidence of VTE were observed between any group. Conclusion. The addition of oral TXA for 24 hours postoperatively does not reduce blood loss beyond that achieved with a single 1 g IV perioperative dose alone. There may be a clinically relevant difference in patients with a normal BMI, which warrants further investigation. Critically, there were no safety issues in patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease. Cite this article: Bone Joint J 2021;103-B(7):1197–1205

Aims. To investigate the bone penetration of intravenous antibiotic prophylaxis with flucloxacillin and gentamicin during hip and knee arthroplasty, and their efficacy against Staphylococcus (S.) aureus and S. epidermidis. Patients and Methods. Bone samples from the femoral head, neck and acetabulum were collected from 18 patients undergoing total hip arthroplasty (THA) and from the femur and tibia in 21 patients during total knee arthroplasty (TKA). The concentration of both antibiotics in the samples was analysed using high performance liquid chromatography. Penetration was expressed as a percentage of venous blood concentration. The efficacy against common infecting organisms was measured against both the minimum inhibitory concentration 50, and the more stringent epidemiological cutoff value for resistance (ECOFF). Results. The bone penetration of gentamicin was higher than flucloxacillin. Relative to ECOFF, flucloxacillin concentrations were effective against S. aureus and S. epidermidis in all THAs and 20 (95%) TKAs. Gentamicin concentrations were effective against S. epidermidis in all bone samples. Gentamicin was effective against S. aureus in 11 (61.1%) femoral neck samples in THA. Effective concentrations of gentamicin against S. aureus were only achieved in four (19%) femoral and six (29%) tibial samples in TKA. Conclusion. Flucloxacillin and gentamicin were found to penetrate bone during THA and TKA. Gentamicin was effective against S. epidermidis in both THA and TKA, while levels were subtherapeutic against S. aureus in most TKAs. Bone penetration of both antibiotics was less in TKA than THA, and may relate to the use of a tourniquet. Using this antibiotic combination, effective cover against the two common infective organisms was achieved in all THAs and all but one TKA. Cite this article: Bone Joint J 2017;99-B:358–64

Tranexamic acid is a fibrinolytic inhibitor which reduces blood loss in total knee replacement. We examined the effect on blood loss of a standardised intravenous bolus dose of 1 g of tranexamic acid, given at the induction of anaesthesia in patients undergoing total hip replacement and tested the potential prothrombotic effect by undertaking routine venography. In all, 36 patients received 1 g of tranexamic acid, and 37 no tranexamic acid. Blood loss was measured directly per-operatively and indirectly post-operatively. Tranexamic acid reduced the early post-operative blood loss and total blood loss (p = 0.03 and p = 0.008, respectively) but not the intraoperative blood loss. The tranexamic acid group required fewer transfusions (p = 0.03) and had no increased incidence of deep-vein thrombosis. The reduction in early post-operative blood loss was more marked in women (p = 0.05), in whom this effect was dose-related (r = −0.793). Our study showed that the administration of a standardised pre-operative bolus of 1 g of tranexamic acid was cost-effective in reducing the blood loss and transfusion requirements after total hip replacement, especially in women

Aims. The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA). Patients and Methods. A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE). Results. The mean HBL was significantly lower in group C (402.13 ml standard deviation (. sd). 225.97) than group A (679.28 ml. sd. 277.16, p < 0.001) or B (560.62 ml . sd. 295.22, p = 0.010). The decrease in the level of Hb between the pre-operative baseline and the level on the third post-operative day was 30.82 g/L (. sd. 6.31 g/L) in group A, 27.16 g/L (. sd. 6.83) in group B and 21.98 g/L (. sd. 3.72) in group C. This decrease differed significantly among the three groups (p < 0.01). The mean level of CRP was significantly lower in group C than in the other two groups on the second (p ≤ 0.034) and third post-operative days (p ≤ 0.014). The levels of IL-6 were significantly lower in group C than group A on the first three post-operative days (p = 0.023). The mean length of stay was significantly lower in group C than group A (p = 0.023). No VTE or other adverse events occurred. Conclusion. Multiple boluses of IV-TXA can effectively reduce HBL following primary THA. A regime of three boluses leads to a smaller decrease in the level of Hb, less post-operative inflammation and a shorter length of stay in hospital than a single bolus. Cite this article: Bone Joint J 2017;99-B:1442–9

A total of 57 patients, aged between 23 and 86 years, with complex regional pain syndrome (CRPS) type 1 nine weeks after an isolated closed fracture of the distal radius, was randomised to receive either serial intravenous regional blockade (IVRB) with 15 mg of guanethidine in 30 ml of 0.5% prilocaine or serial IVRB with 30 ml of normal saline at weekly intervals until the tenderness in their fingers had resolved or they had received a maximum of four IVRBs. The analgesic efficacy was assessed at 24 hours, 48 hours and one week after each procedure by the dolorimetry ratio and verbal pain scores, and at intervals up to six months after the fracture. There was no significant difference in the number of IVRBs administered or in finger tenderness, stiffness or grip strength between the two groups. The guanethidine group experienced more pain in the affected hand (p = 0.025) and at six months had more vasomotor instability (p < 0.0001) compared with the control group. IVRB using guanethidine offers no significant analgesic advantage over a normal saline placebo block in the treatment of early CRPS type 1 of the hand after fracture of the distal radius. It does not improve the outcome of this condition and may delay the resolution of vasomotor instability when compared with the placebo

Bone-marrow oedema can occur both in isolation and in association with necrosis of bone, but it has not been shown whether each respond to the same methods of treatment.

We treated 16 patients with isolated oedema and 17, in which it was associated with necrosis of the proximal femur, with the prostacyclin derivative iloprost, which has been shown to be effective in the idiopathic form. The Harris hip score, the range of movement, the extent of the oedema as measured by MRI, pain on a visual analogue scale and patient satisfaction were recorded before and subsequent to treatment.

In both groups, we were able to show a significant improvement (p < 0.001) in these observations during the period of follow-up indicating that iloprost will produce clinical improvement in both circumstances.