Abstract. Introduction. Multiple strategies, used either in isolation or combination, are available to reduce the need for post-operative blood transfusion in joint replacements. Amongst them, the use of tranexamic acid (TXA) has been rising and this study was conducted to compare the efficacy of topical and intravenous TXA in bilateral total knee replacement patients. Materials and methods. Randomised prospective study with 120 patients (male: female: 25:95) undergoing bilateral TKA. Patients were divided into two groups A and B after computer randomization, who received intravenous or topical (intra-articular) TXA respectively. Results. The average haemoglobin loss in intravenous group was 90.2379 g/L as compared to 39.137 g/L in topical group (p < 0.005). Moreover, there was reduction in blood loss in topical (330.1602 ml) as compared to intravenous group (764.9622 ml). The blood transfusion rate was more for the intravenous group (average 1.73 units) than for the topical group (average 0.75, unit). WOMAC score at 6 weeks in the intravenous group was 12.50, and in the topical group was 7.23 (p value < 0.001). Conclusion. Topical TXA is better than intravenous TXA for reduction of blood loss, which also reduces the need for blood transfusion in bilateral TKA patients

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. Study Design: Randomized controlled trial. Duration of Study: Six months, from May 2019 to Nov 2019. Seventy-eight patients were included in the study. All patients undergoing unilateral primary total knee replacement were included in the study. Exclusion criteria were patients with hepatitis B and C, history of previous knee replacement, bilateral total knee replacement, allergy to TXA, Hb less than 11g/dl in males and less than 10g/dl in females, renal dysfunction, use of anticoagulants for 7 days prior to surgery and history of thromboembolic diseases. 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). At 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). About 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

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

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

Arthroplasty in patients who are intravenous drug abusers presents a complex challenge, frequently requiring intervention at a younger age. The cohort suffer increased complication rates due to significant co-morbidities and poor engagement in medical services, in comparison to other patients undergoing lower limb arthroplasty. Multiple small studies show arthroplasty in this patient cohort is associated with high complication and mortality rates. A search of electronic databases were undertaken with the assistance of the library services from the Rotherham NHS Foundation Trust, including Chocraine, SCOPUS and PubMed. Abstracts were reviewed and relevant studies extracted for full review. Full text articles were reviewed based on strict inclusion and exclusion criteria. Searches identified Two thousand and forty-four papers; twenty-seven studies were identified for full review of the paper based on the inclusion criteria above. From this, nine studies were deemed appropriate to for data extraction. These nine papers present one hundred and thirty-two cases of lower limb arthroplasty, fifty nine Total Knee Arthroplasty and seventy three Total Hip Arthroplasty. From this the authors examined incidences of implant failure due to infection, revision, mortality, dislocation, aseptic loosening, peri-prosthetic fracture, or other causes. Of these, 58% of patients (n = 77) with a history of intravenous drug abuse suffered some form of significant complication; 4% of this cohort (n = 5) were lost to follow up. Infection was reported in 32% of cases and a mortality rate of 4.7%. The rising demand of lower limb arthroplasty for intra-venous drug abusers presents a very real problem for the modern Orthopaedic surgeon. Within the studies examined, more than half report implant failure. This study synthesises the available literature regarding treatment of these patients to help facilitate decision making and informed consent

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

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

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

Tranexamic acid (TXA) is an inexpensive antifibrinolytic. Currently there are no national guidelines in the UK that promote the use of TXA in femoral fragility fracture (FFF) management. The aim of the study was to determine whether intra-operative intravenous TXA affects the requirement for post-operative blood transfusion following FFF surgery. A prospective non-randomized case-control study of consecutive FFF admitted to the study centre was performed. 361 patients were included in the study (mean age 81.4yrs; mean BMI 23.5; 73.7% female). TXA was given at the discretion of the operating surgeon, with 178 (49%) patients receiving TXA. Patient demographics, surgical management, peri-operative haemoglobin (Hb) and haematocrit, intravenous TXA use, and requirement for blood transfusion were recorded prospectively. Percentage fall in Hb from preoperative level was calculated at postoperative day one. Calculated-blood-loss (CBL) was determined using the Nadler and Gross formulae. The groups were well matched in terms of patient demographics, injury types and surgical management. The requirement for postoperative blood transfusion was significantly reduced in the TXA group: 15/178 (8.4%) compared to 58/183 (31.7%) (p<0.001; Chi square). TXA significantly reduced both the percentage fall in Hb (mean difference 4.3%, p<0.001) and the CBL (mean difference -222ml, p<0.001). There was no difference in venous thrombosis embolism events between the groups. Intra-operative intravenous TXA during the surgical management of FFF significantly reduced rate of transfusion, CBL and the percentage drop in HB

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

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

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

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

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

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

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

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. 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