Hemostasis of Suprapatellar Synovium and Arthrotomy Site Prior to Tourniquet Inflation Reduce Blood Loss After Total Knee Arthroplasty: A Randomized Controlled Trial

What's New in Adult Reconstructive Knee Surgery.

This study involved a meta-analysis of 36 published studies to examine the efficacy of intravenous (IV) and intra-articular (IA) tranexamic acid (TXA) in reducing blood loss, drain output, thromboembolic complications, and hospital stay following total hip and total knee arthroplasty. This study also evaluated whether treatment with a combination of both IA and IV TXA has an effect on these outcomes. Lastly, this study attempted to analyze the method and technique of TXA administration in order to establish a best practice for its use in reducing overall blood loss in arthroplasty procedures. MEDLINE, Embase, and the Cochrane Library database were screened. Studies comparing IV TXA with IA TXA or with combined IV and IA TXA were included. Data including total blood loss, drain output, thromboembolic complications, and hospital stay, where available, were analyzed using meta-analysis with fixed effects. Results are presented as the standardized mean difference (SMD), and meta-regression was employed to explore plausible demographic contributions to heterogeneity. Twenty-eight randomized controlled trials, 3 prospective cohort studies, and 5 retrospective cohort studies with 5,499 patients were included in this review. IA administration during total knee arthroplasty showed a significant advantage in terms of total blood loss (SMD = -0.14, 95% confidence interval [CI] = -0.027 to -0.02, I = 78.2%) and drain output (SMD = -0.30, 95% CI = -0.43 to -0.18). There was no significant difference between IV and IA administration in total hip arthroplasty. Combined IA plus IV TXA was associated with a significant reduction in blood loss versus IV TXA alone in both total knee arthroplasty and total hip arthroplasty. IV TXA dosing varied, as 14 (39%) of the studies used a weight-based approach while 22 (61%) used a standard dose. Twenty-seven (96%) of 28 studies of IA administration used standard dosing while 1 study followed a weight-based protocol. There was no difference in symptomatic thromboembolic complications, with overall rates in total knee arthroplasty and total hip arthroplasty of 1.0% and 1.0% for IV administration and 1.1% and 0.3% for IA administration, respectively. There was no difference in length of hospital stay for IV versus IA TXA administration. IA TXA, either alone or in conjunction with IV TXA, reduces total blood loss and/or drain output in total knee arthroplasty and total hip arthroplasty. Optimal methodology remains to be clarified; however, there are substantial economic benefits of utilizing either IV or IA TXA, with greater cost benefits when using IA TXA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Update This article was updated on February 6, 2019, because of a previous error. On page 105, in the subsection titled “Outcomes and Design” the sentence that had read “Furthermore, in a retrospective review, Houdek et al. 48 , at a mean follow-up of 8 years, demonstrated improved survivorship of 9,999 metal-backed compared with 1,645 all-polyethylene tibial components, over all age groups and most BMI categories” now reads “Furthermore, in a retrospective review, Houdek et al. 48 , at a mean follow-up of 8 years, demonstrated inferior survivorship of 9,999 metal-backed compared with 1,645 all-polyethylene tibial components, over all age groups and most BMI categories.” An erratum has been published: J Bone Joint Surg Am. 2019 Mar 20;101(6):e26.

The Efficacy Comparison of Tranexamic Acid for Reducing Blood Loss in Total Knee Arthroplasty at Different Dosage Time

Tranexamic acid (TXA) reduces blood loss and transfusion rates in unilateral total knee arthroplasty (TKA), but there is limited data regarding its efficacy in bilateral TKA. This study reports the impact TXA has on clinical outcomes and hospital cost of care in simultaneous, primary bilateral TKA. The 449 patients were retrospectively reviewed. Primary outcomes included the rates of allogeneic and autologous blood transfusion. Secondary outcomes included hospital length of stay (HLOS), post-hospital discharge disposition, 30-day thromboembolic events (TEE), and mean hospital cost of care. Total direct medical costs were obtained from an institutional research database and adjusted to nationally representative unit costs in 2013 inflation-adjusted dollars. Our study revealed that in patients undergoing simultaneous bilateral TKA, TXA use was associated with reduced allogeneic (OR 0.181, 95% CI 0.090-0.366, p < 0.001) and combined allogeneic and autologous transfusion rates (OR 0.451, 95% CI 0.235-0.865, p = 0.017). TXA was associated with a HLOS reduction of 0.9 days (β-coefficient −0.582, 95% CI −1.008-−0.156, p = 0.008), an increased likelihood of hospital discharge over skilled nursing facility (SNF) (OR 2.25, 95% CI 1.117-4.531, p = 0.023) and reduced total hospital cost of care by 6.45% (p < 0.001), room and board costs by 11.76% (p < 0.001), and transfusion costs by 81.65% (p < 0.001). In conclusion, TXA use in bilateral TKA is associated with lower blood transfusion rates, reduced hospital length of stay, reduced cost of hospital care and skilled nursing facility avoidance.

Many different methods and drain clamping periods have been described in systemic and local tranexamic acid (TXA) applications, and the superiority of the methods to each other has not been clearly demonstrated. The method of local infusion in combined TXA applications may not alter the Hb drop or total or hidden blood loss. We aim to compare two different combined TXA application methods. We retrospectively analyzed 182 patients who underwent total knee arthroplasty between 2018 and 2021. Patients over 40 years of age who underwent TKA for degenerative knee arthritis were included in the study. Unicondylar, revision, or bilateral arthroplasties and patients with the cardiovascular or cerebrovascular disease were excluded from the study. All patients in the study received 1 g TXA intravenously half an hour before the incision. For the first group, 1 g TXA was given intra-articularly at the drain site after closure, and the clamp was kept closed for 1 hour. In the second group, the drain was clamped for an additional 6 hours, and a 1 g intravenous dose was administered at the 5th hour postoperatively. No local applications were used in the control group. Total, hidden, and visible blood loss (total blood loss, hidden blood loss, visible blood loss), postoperative decreases in hemoglobin and hematocrit level (ΔHgb, ΔHtc), blood transfusion rates, and hospital stay durations were evaluated. There were 72 patients in the first group, 52 in the second, and 58 in control. A total of 37 patients received one or more blood transfusions postoperatively, and there was no statistical difference in the need for blood transfusions between the groups (P = .255). Although a statistically significant difference (P = .001) in total blood loss, hidden blood loss, visible blood loss and ΔHgb values was observed between the groups, the difference between the first and second groups was insignificant (P = .512). The duration of hospital stay was observed to be less in the first and second groups (P = .024). Local and systemic TXA applications were observed to be more effective than only systemic applications in reducing blood loss after total knee arthroplasty, regardless of the local method.

This issue of TRANSFUSION features two clinical trials on the use of tranexamic acid (TXA) in joint replacement surgery. The first study examines the use of TXA for reducing autologous blood transfusion in total knee or hip replacement surgery.1 The second study reports the effect of TXA on allogeneic blood transfusion for two-staged bilateral total knee replacement surgery.2 The first study is a double-blinded randomized placebo controlled trial in which Oremus and colleagues1 compared TXA with placebo to evaluate the efficacy of TXA to reduce autologous transfusion of shed blood in unilateral primary total knee or hip replacement. Ninety-eight primary hip or primary knee replacement patients were randomly allocated to receive an intraoperative intravenous (IV) dose of 1 g of TXA or placebo 15 minutes before skin incision for total hip replacement or 15 minutes before tourniquet release for total knee replacement. After 3 hours, a second dose of 1 g of TXA or an equivalent volume of placebo (saline) was administered IV. The minimum volume of retransfusion was set at 250 mL and a transfusion trigger of hemoglobin (Hb) level of less than 8 or 8 to 10 g/dL with symptoms of anemia. Only 10.2% in the TXA group versus 85.7% in the placebo group received autologous transfusion. The TXA group had a 75% lower requirement for autologous transfusion than the placebo group. The median total external blood loss during the first 24 hours was 320 mL (80-930 mL) in the TXA group versus 970 mL (100-2600 mL) in the placebo group. This study also examined the safety profile of TXA by measuring hemodynamic changes during administration of TXA and performed postoperative screening for deep vein thrombosis (DVT). Clinical assessment for DVT was performed three times a day and ultrasonography, fibrinogen, and D-dimer measurements were performed in suspected cases. The authors did not find any difference in hemodynamic changes or DVT between both groups. In addition, there was no difference in blood loss between the total knee replacement and total hip replacement surgery. This study provides evidence that using TXA with a restrictive transfusion trigger policy can potentially replace the use of an autologous drain system. This protocol can avoid the autologous blood transfusion related complications such as febrile reactions and possible retrograde infection. The use of closed suction drainage for joint replacement surgery is controversial and there is practice variation in whether surgical drains are used. Although the use of a drain is based on individual or institutional practice, evidence has shown that the use of a closed system suction drainage increases the total blood loss after joint replacement surgery.3 At the same time, a recent meta-analysis has confirmed that autologous shed blood transfusion is an effective method to reduce allogeneic blood transfusion.4 Other techniques used to reduce the blood loss are clamping the drain, retrograde injection of TXA through the drain, and closure without a drain.5 The current study by Oremus and coworkers suggests that TXA could potentially eliminate the need for surgical drains and autologous shed blood transfusion. The cost-effectiveness of using TXA rather than autologous transfusion of shed blood was not analyzed in this study, although the cost of TXA may be lower. Overall this well-designed randomized controlled trial shows the efficacy of TXA on reducing autologous shed blood transfusion. The second study is a retrospective study in which Kelley and coworkers2 determined the effect of TXA on blood transfusion in patients undergoing bilateral total knee replacement staged 3 days apart. Transfusion rates were compared between patients who did not receive TXA (before the routine use of TXA) and after the institution of TXA for bilateral total knee replacement. The TXA group received 1 g of TXA IV 15 minutes before incision and 1 g IV before tourniquet release. The main findings were the TXA group had lower mean blood loss than the non-TXA group (373.8 ± 264.6 mL vs. 871.6 ± 457.7 mL, respectively). The blood transfusion rate was lower (43.1% vs. 71.4%) in the TXA group and the amount of allogeneic blood transfusion was lower (0.64 ± 0.84 units vs. 1.53 ± 1.30 units) in the TXA group. In addition, the TXA group had significantly higher Hb level on Day 1 and Day 2 with each stage of total knee replacement. Otherwise there was no difference in postoperative complications including infection, venous thromboembolism, reoperation, hematoma, or pre- and postoperative Knee Society score and range of movement. Since this study was retrospective, routine screening for venous embolism was not done. The transfusion trigger was 9 g/L for the first surgery and 8 g/L for the second surgery. These two studies add to the growing literature supporting the efficacy of TXA for reducing blood loss6, 7 and blood transfusion in joint replacement surgery. Surgical trauma and the use of a tourniquet have been shown to activate fibrinolysis. TXA is a lysine analog that helps to prevent fibrinolysis in conditions that promote fibrinolysis. TXA is relatively inexpensive, easy to administer, and more cost-effective than transfusion and other blood conservation techniques. Existing studies in the orthopedic surgical literature have not shown an increase in adverse events such as thromboembolic complications with the use of TXA for joint replacement surgery. Although the study designs differ, both current studies used the same total dose of TXA and used closed suction drain systems. The total dose of TXA used in both studies was 2 g, but the timing of administration was different. The timing of administration and dosage of TXA have varied in previous studies. A recent study found a preoperative and intraoperative IV dose of TXA was more effective than a single dose of TXA given intraoperatively or an intraoperative dose followed by a postoperative dose.8 These authors also concluded that a single dose with local application was more effective than a single dose administered IV.8 The optimal dose, timing of administration, mode of administration, and duration of treatment have not been determined. A recent systematic review and meta-analysis concluded that the effect of TXA on blood loss varied with the timing of administration of TXA, but the extent of this variation was small, and the authors questioned the clinical importance of this variation.9 The authors also found a lack of a dose–response relationship of TXA, with a total dose of about 14 mg/kg (approx. 1 g) appearing to be sufficient. However, these authors did not specifically examine joint replacement surgery, but included different types of surgery. Most of the blood loss in total knee replacements occurs during the first few hours after surgery.10 A recent pharmacokinetic study showed that peak fibrinolytic activity occurred at 6 hours from the incision time for both total hip and total knee replacement, and the fibrinolysis activity persisted for 18 hours.11 This finding supports a multiple dose regime or a postoperative infusion as the most effective way to reduce blood loss with use of TXA in joint replacement surgery. However, this protocol must be balanced with the high risk for DVT in this patient population. These studies support the use of TXA to reduce blood loss and transfusion in joint replacement surgery. The optimal timing, dose, duration of treatment, and route of administration of TXA, however, remain uncertain. There is a need for more pharmacokinetics studies to optimize the use of TXA to reduce blood loss and blood transfusion, while minimizing any potential adverse effects in joint replacement surgery. These studies should be encouraged by the transfusion medicine community since TXA appears to be a useful pharmacologic alternative to transfusion in orthopedic surgery. None.

In addition to the surface hemorrhage of cancellous bone after large-area osteotomy, the intramedullary hemorrhage after the reamed knee joint is also a major cause of postoperative bleeding after total knee arthroplasty (TKA). This study evaluated the efficacy and safety of bone wax application at different time points of prone hemorrhage to reduce perioperative blood loss. From August 2023 to December 2023, 150 patients undergoing primary unilateral TKA were included in this prospective, randomized controlled trial, patients were randomly divided into three groups: group A, after autogenous osteotomy plug was used to fill the femoral medullary cavity, the residual space was sealed with bone wax and the exposed cancellous bone surface around the prosthesis was coated with bone wax after the prosthesis adhesion; group B, only the exposed cancellous bone surface around the prosthesis was coated with bone wax; and group C, no bone wax was used. The primary outcome was total perioperative blood loss. Secondary outcomes included occult blood loss, postoperative hemoglobin reduction, blood transfusion rate, lower limb diameter, and knee function, while length of hospital stay was recorded. Tertiary outcomes included the incidence of postoperative related adverse events. The total blood loss in group A (551.5 ± 224.5 mL) and group B (656.3 ± 267.7 mL) was significantly lower than that in group C (755.3 ± 248.3 ml, p < 0.001), and the total blood loss in group A was also lower than that in group B (p < 0.05). There were also significant differences in the reduction of hemoglobin level and hidden blood loss among the three groups (p < 0.05). However, there was no significant improvement in postoperative lower limb swelling, knee joint activity and hospitalization time; there was no significant difference in the incidence of complications such as thromboembolism. The use of bone wax in TKA can safely and effectively reduce perioperative blood loss and hemoglobin drop rate, and multiple use at time points during the operation when blood loss is prone to occur can produce more significant hemostatic effect.

Purpose: Postoperative blood loss is a common complication following total knee arthroplasty (TKA). The authors aimed to analyze the significance of open versus closed-box prostheses in reducing blood loss after TKA. Methods: PubMed, Cochrane, Scopus, and Web of Science were searched. Observational studies and clinical trials comparing the effect of open-box versus closed-box prostheses on blood loss following TKA were included. The primary outcome was total blood loss following TKA. Secondary outcomes included average transfused units and total operation time. Continuous data were represented as mean difference (MD) and CI, while dichotomous data were presented as odds ratio (OR) and CI. RevMan software version 5.4 was used to conduct the analysis. Results: Four studies with a total number of 687 patients were included. The pooled analysis showed a statistically significant association between closed-box and decreased total blood loss following TKA compared with open-box (MD=173.19, 95% CI=88.77–257.61, P value &lt;0.0001). Similar findings were reported in unilateral TKA (MD=190.63, 95% CI=70.91–310.35, P value=0.002), and bilateral TKA (MD=160.79, 95% CI=61.70–359.86, P value=0.001). There was no significant difference between open and closed-box regarding average transfused units (MD=0.02, 95% CI=−0.07–0.11, P value=0.68), blood transfusion rate (OR=1.38, 95% CI=0.85–2.26, P value=0.20), length of stay (MD=0.06, 95% CI=−0.27 to 0.38, P value=0.74), and total operation time (MD=1.08, 95% CI=−4.62 to 6.79, P value=0.71). Conclusion: Closed-box reduces the total blood loss following unilateral and bilateral TKA. More studies are warranted to explore the benefits of Closed-box in patients with high bleeding susceptibility.

BackgroundThe optimal dosage and administration approach of tranexamic acid (TXA) in primary total knee arthroplasty (TKA) remains controversial. In light of recently published 14 randomized controlled trials (RCTs), the study aims to incorporate the newly found evidence and compare the efficacy and safety of intra-articular (IA) vs. intravenous (IV) application of TXA in primary TKA.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched for RCTs comparing IA with IV TXA for primary TKA. Primary outcomes included total blood loss (TBL) and drain output. Secondary outcomes included hidden blood loss (HBL), hemoglobin (Hb) fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time.ResultIn all, 34 RCTs involving 3867 patients were included in our meta-analysis. Significant advantages of IA were shown on TBL (MD = 33.38, 95% CI = 19.24 to 47.51, P < 0.001), drain output (MD = 28.44, 95% CI = 2.61 to 54.27, P = 0.03), and postoperative day (POD) 3+ Hb fall (MD = 0.24, 95% CI = 0.09 to 0.39, P = 0.001) compared with IV. There existed no significant difference on HBL, POD1 and POD2 Hb fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time between IA and IV.ConclusionIntra-articular administration of TXA is superior to intravenous in primary TKA patients regarding the performance on TBL, drain output, and POD3+ Hb fall, without increased risk of perioperative complications. Therefore, intra-articular administration is the recommended approach in clinical practice for primary TKA.

Objective To investigate the effect and safety of topical tranexamic acid(TXA) plus cocktail analgesic for reducing blood loss during total knee arthroplasty (TKA). Methods A prospective case control study was made on 60 patients scheduled to undergo TKA because of knee injuries between August 2015 to June 2016. There were 13 males and 47 females, with the mean age of 65.5 years (range, 51-80 years). Traumatic arthritis occurred in 44 patients and degenerative arthritis in 16 patients. The patients were assigned to separate cocktail analgesic group (Group A, n=30) and topical TXA plus cocktail analgesic group(Group B, n=30), according to the random number table. Patients in Group A received multiple-point intra-articular cocktail analgesic injection before implantation of the prosthesis in TKA. While patients in Group B received multiple-point intra-articular TXA plus cocktail analgesic injection before implantation of the prosthesis. Between-group differences were compared with respect to intraoperative blood loss, hemoglobin change (Hb), haematocrit (Hct), postoperative drainage, total blood loss, hidden blood loss, blood transfusion rate, Hospital for Special Surgery (HSS) score, incidence of deep venous thrombosis (DVT) and other complications. Results All patients were followed up for 3 months. Perioperative Hb reduction in Group B was 18.5 (13.0, 26.0)g/L, less than 23.0 (21.0, 35.5)g/L in Group A (P 0.05). Conclusion Topical TXA plus cocktail analgesic can reduce blood loss during perioperative period in TKA, without increasing the risk of DVT. Key words: Tranexamic acid; Injection, intra-articular; Arthroplasty, replacement, knee; Postoperative bleeding

Comparison of oral versus intravenous application of tranexamic acid in total knee and hip arthroplasty: A systematic review and meta-analysis

BackgroundBlood loss and deep vein thrombosis (DVT) are important complications after total knee arthroplasty (TKA). Topical tranexamic acid (TXA) effectively reduces wound bleeding but may elevate the risk of DVT. In contrast, rivaroxaban potently prevents DVT but has been associated with bleeding complications. The simultaneous use of topical TXA and rivaroxaban in TKA has not been much investigated.MethodsA retrospective cohort study was conducted with two consecutive groups of patients who underwent TKA. Intraoperatively, one group (RVTX group) received topical, intraarticular TXA, while the other (RV group) did not. Both groups were administered rivaroxaban postoperatively for 14 days and underwent Doppler ultrasound for DVT screening. After propensity score matching, both groups consisted of 52 patients (104 patients in total) and were compared regarding total drain output, nadir haemoglobin (Hb), maximum Hb decrease, calculated total blood loss, transfusion rate, and incidence of DVT and wound complications.ResultsBoth groups showed no significant differences in the propensity-matched variables of age, sex, body mass index, American Society of Anesthesiologists physical status score, and preoperative Hb. The RVTX group showed a significantly higher nadir Hb (p < 0.001), lower drain output (p < 0.001), Hb decrease (p = 0.015), total blood loss (p < 0.001), and rate of transfusion (p < 0.001) and fewer wound complications (p = 0.027). However, the incidence of DVT (p = 1.000) did not differ significantly between the two groups, and all cases were asymptomatic.ConclusionsThe combined use of intraarticular topical TXA with rivaroxaban in patients undergoing TKA is a safe and effective method to reduce blood loss, the need for transfusion, and wound complications without elevating the risk of DVT.

Tranexamic acid (TXA) has been shown to reduce blood loss during total knee arthroplasty (TKA) and total hip arthroplasty (THA), but the most effective administration method has yet to be determined. This systematic review and meta-analysis aimed to compare topical and systemic TXA administration to reduce operative blood loss. MEDLINE, Embase, and Cochrane CENTRAL were screened for randomized controlled trials comparing topical and systemic TXA for patients who underwent elective TKA and THA. The primary outcome was the total volume of operative blood loss, and the secondary outcomes were postoperative transfusion requirements, hemoglobin drop, hospital length of stay, and the frequencies of the main adverse events (infections and thromboembolic events). Data pooling was performed using RStudio. Subgroup analyses compared outcomes between TKA and THA. Fifty-nine randomized controlled trials with a total of 6,791 patients were included in this review. Data analysis showed no significant difference between topical and systemic TXA application in terms of total blood loss (Hedges g = 0.11; 95% confidence interval [CI], -0.04 to 0.26; I 2 = 82.4%). There was also no significant difference between the 2 groups in hemoglobin drop, hospital length of stay, and transfusion requirements. Subgroup analysis showed that patients undergoing TKA who received topical TXA had a significant reduction in total blood loss (g = 0.19; 95% CI, 0.00 to 0.38; I 2 = 85%; p = 0.046) compared with those who received systemic TXA. Topical and systemic TXA were equally effective in reducing blood loss in the analysis in which THA and TKA were combined. However, in TKA, topical application significantly reduced blood loss compared with systemic administration, while the reverse was true in THA. Further research is still necessary to find the optimal TXA dosage and administration route. Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Efficacy of a Single Dose and an Additional Dose of Tranexamic Acid in Reduction of Blood Loss in Total Knee Arthroplasty