Intraoperative blood loss has always been an important issue in joint replacement surgery. Clinicians have been pioneering various methods dedicated to reducing intraoperative bleeding and lowering postoperative transfusion rates. Studies have found that preoperative use of tranexamic acid is effective in reducing perioperative blood loss and decreasing the rate of blood loss. Tranexamic acid is a synthetic class of drugs that reduces blood loss by inhibiting fibrinolysis and thrombotic degradation.
The clinical use of tranexamic acid as a measure of perioperative blood management in total joint replacement has gained some acceptance, but the exact dose and manner of use remains controversial. Recently J stuart Melvin et al. wrote an article in the JAAOS journal on the use of tranexamic acid in the perioperative period.
Basic knowledge
With an annual volume of over one million arthroplasties performed worldwide, intraoperative and postoperative blood loss is generally high, with postoperative transfusion rates reported in the literature ranging from 11% to 67%, increasing not only the cost of surgery and the risk of disease transmission, but also the probability of peri-articular prosthetic infection.
Traditional clinical approaches to reduce perioperative blood loss include preoperative blood reserve, hemodilution, controlled intraoperative hypotension, and postoperative erythropoietin application. Recently, pharmacologic modalities to reduce blood loss are gaining attention, such as intravenous and local application of tranexamic acid analogs.
Tranexamic acid is a synthetic drug that inhibits fibrinolysis and thrombotic degradation. (Surgical trauma, for example, leads to a stress response and hyperfibrinolysis in the blood. Tranexamic acid reversibly binds to the lysine site on fibrinogen in the blood, preventing the activation of protease, fibrinogen, and thus ultimately inhibiting fibrin degradation).
The types of tranexamic acid preparations include intravenous, oral, and topical applications, and are widely used in cardiology, obstetrics and gynecology, gastrointestinal surgery, neurosurgery, and orthopedics. Total joint replacement doses are typically 1-2 g, while other surgical procedures range from 1 g (cardiac) to 6 g (subarachnoid hemorrhage), with application times ranging from a few days to 3 weeks. It is important to note that tranexamic acid is only clinically indicated for hemophilia hemorrhage prophylaxis, so strictly speaking, most tranexamic acid applications are currently over-indicated.
Tranexamic acid in primary total knee replacement
There is now much clinical literature to support the use of tranexamic acid in total knee arthroplasty to reduce blood loss and transfusion rates. Tranexamic acid can be administered intravenously, topically, or orally, depending on the mode of application.
A recent systematic evaluation found that the perioperative intravenous application of tranexamic acid during primary total knee arthroplasty reduced blood loss by approximately 500 ml and transfusion by 1.43 units. Most of the studies included in this systematic evaluation (14/15) administered low doses of intravenous tranexamic acid (10-50 mg/kg), with only one study using a high dose (150 mg/kg).
Topical application of tranexamic acid in joint replacement is also widely supported by the literature. Georgiadis reported 2.0 g of tranexamic acid + 75 ml of saline with intra-articular immersion for 5 min; Chimento advocated 3 g + 100 ml of saline with intra-articular immersion; Mutsuzaki et al. suggested 1 g of tranexamic acid dissolved in saline and injected retrogradely into the joint cavity through a drainage tube for 1 hour. The drainage tube was clamped for 1 hour. A Meta-analysis concluded that intra-articular topical tranexamic acid of 2 g or more was effective in reducing postoperative blood transfusion rates.
Two studies compared the effectiveness of topical tranexamic acid with intravenous tranexamic acid in reducing blood loss; Huang et al. It was found that intravenous tranexamic acid was more effective in reducing blood loss, and intra-articular injection was the most effective in reducing postoperative drainage.
The effect of oral tranexamic acid in reducing bleeding during arthroplasty has also been reported in the literature.Irwin compared the effect of 15 mg/kg intravenous and 25 mg/kg oral tranexamic acid in controlling bleeding and found that oral tranexamic acid did not increase the incidence of side effects and reduced bleeding. A randomized controlled trial completed by Alipour et al. also demonstrated that 1 g of tranexamic acid given orally 2 hours before surgery and every 6 hours for 18 hours after surgery was effective in reducing bleeding.
Tranexamic acid in primary total hip arthroplasty
Similar to total knee arthroplasty, the use of tranexamic acid in total hip arthroplasty has been well documented to reduce blood loss.
The use of tranexamic acid in total hip arthroplasty is similar to that of total knee replacement, but the doses reported in the literature vary from 1 g intravenously preoperatively by Rajesparan et al. to 10 mg/kg on a body weight basis, once preoperatively and twice postoperatively at 8-hour intervals by Niskanen et al. The topical dose recommended by yue et al. is 3 g.
Application in total hip or total knee revision
The perioperative use of tranexamic acid in total hip or total knee revision is poorly reported in the literature, which I believe is mainly related to the low number of these procedures. However, with reference to the results that tranexamic acid is effective in reducing perioperative bleeding and transfusion rates in primary arthroplasty, it is appropriate to infer that the perioperative use of tranexamic acid in revision arthroplasty may reduce perioperative bleeding and transfusion rates.
Dose and timing of intravenous use
Available literature reports show more variation in the manner, dose, and timing of tranexamic acid use, and it is difficult to give a definitive conclusion, but a few general application lessons can be summarized based on available literature reports.
Most of the literature reports the use of 10-20 mg/kg in the perioperative period of joint replacement or the administration of a fixed dose of 1 g. However, the exact dose remains highly controversial, with some literature finding that higher doses reduce bleeding, but others suggesting that the dose level does not affect the amount of bleeding. A recent systematic review of the literature on tranexamic acid in multiple fields (doses ranging from 5.5 mg-300 mg/kg) found that there was no necessary association between tranexamic acid dose and patient blood loss, and that a fixed dose of 1 g or 14 mg/kg body weight was sufficient for adults. However, another systematic evaluation concluded the opposite, that total dose use of more than 4 g in total knee arthroplasty reduced transfusion rates.
In patients undergoing total joint replacement, the timing and duration of tranexamic acid administration plays a very important role in reducing blood loss and transfusion rates; Tanaka et al. found that a tranexamic acid drip 10 min before the start of surgery was more effective than a tranexamic acid drip 10 min before tourniquet release, and Imai et al. reported similar results.
Imai et al. also reported similar results. It has been suggested that giving tranexamic acid again postoperatively is more relevant than exploring how to give the right dose of tranexamic acid at once. Multiple doses of tranexamic acid can achieve better hemostasis than a single dose. A Meta-analysis of 18 randomized, controlled studies of 1094 total knee replacements concluded that postoperative readministration of tranexamic acid was more effective in reducing transfusion rates than single administration of tranexamic acid, and Iwai, Tananka et al. suggested that postoperative readministration of tranexamic acid was more effective in reducing postoperative blood loss and lowering transfusion rates.
Based on the evidence from these studies, the authors suggest that an intravenous dose of 10-20 mg/kg is most appropriate for tranexamic acid in patients undergoing arthroplasty; tranexamic acid given once before the start of joint surgery and again at least once afterwards is consistent with the metabolic profile of tranexamic acid: in healthy humans, 10 mg/kg is given at a blood concentration of 10-15 ng/ml (a concentration that is The blood concentration is 10-15 ng/ml (the optimal concentration for fibrinolytic inhibition) and is maintained for approximately 3-4 hours in healthy humans. Alternatively, tranexamic acid should be administered intravenously at the prescribed dose and at the prescribed time: 1 g before the start of the procedure and 1 g before the closure of the incision at the end of the procedure.
Tranexamic acid in patients at high risk of thrombosis
Most studies on the clinical use of tranexamic acid have excluded patients with a high thrombotic risk (history of previous stroke, previous cardiac stenting, previous deep vein thrombotic events, previous heart attack, previous coronary artery bypass grafting, or thrombogenic predisposition such as protein C deficiency), making it difficult to assess the safety of tranexamic acid in this group of patients.
A study of tranexamic acid in 1102 ASA-rated III-IV total joint arthroplasty patients found that 240 patients at high risk of thrombosis treated with tranexamic acid did not have an increased risk of symptomatic venous thrombosis at 30 days postoperatively. However, there are too few relevant studies to draw relatively definitive conclusions about this. Therefore, it has been suggested that topical tranexamic acid may be more appropriate for such patients at high thrombotic risk.
Tranexamic acid and deep vein thrombosis prophylaxis
A great deal of clinical attention is currently being paid to the prevention of deep vein thrombosis after arthroplasty, and a number of relevant drugs are being used for venous thrombosis prophylaxis. There is no documented evidence that the use of tranexamic acid in combination with anticoagulant drugs increases the incidence of DVT.
Contraindications, Precautions, Complications
Contraindications to the use of tranexamic acid in joint replacement include allergy, active thrombophilia, and epilepsy. The reason tranexamic acid is not used in epileptic disorders is that the drug penetrates the blood-brain barrier and induces seizures through glycine receptor binding, and it has been reported in the literature that application of high doses (50 mg/kg) tends to induce seizures.
It has been reported in the literature that patients with tranexamic acid may experience postoperative visual impairment and impaired color discrimination, making tranexamic acid a relative contraindication for patients with visual impairment. In arthroplasty, tranexamic acid is used in smaller doses and may be less of a concern. Tranexamic acid is metabolized by the kidneys, so care needs to be taken to adjust the dose in patients with impaired renal function.
One of the most important issues in the use of hemostatic drugs, and one of the most important concerns, is the event of deep vein thrombosis. The detection of thrombosis by ultrasound, whole-body CT, perfusion scans, and venography after tranexamic acid administration did not reveal an increased risk of thrombosis. Multiple Meta-analyses also did not find an increased risk of VTE, infection, or other related side effects with tranexamic acid use.
The main points summarized in the full article are as follows.
1. a dose of tranexamic acid is given intravenously before the start of arthroplasty; tranexamic acid is given at least once postoperatively. The specific dose recommended is 10-20 mg/kg, or a fixed dose of 1 g.
2. the hemostatic effect of tranexamic acid is better at doses above 2 g than at lower doses when applied topically.
3. topical application of tranexamic acid as the first choice in patients with a high risk of thrombosis.
4. in the joint replacement population, current research evidence does not find an increased incidence of symptomatic venous thromboembolic events with tranexamic acid application, and there are fewer side events associated with tranexamic acid application.