TXA is a pharmacologic agent that acts through an antifibrinolytic mechanism to stabilize formed clots and reduce active bleeding [6]. Previously reports showed that TXA had a notable role in reducing blood loss and the need for transfusion after TKA, without increasing the risk of DVT [15, 16]. There are many administration routes for TXA, including intravenous administration, intra-articular injection, intramuscular injection and oral administration, among which intravenous administration and intra-articular injection are more commonly used in orthopedic applications [17]. Both intravenous and intra-articular applications of TXA have been reported to reduce drainage blood volume and hemarthrosis after ACLR, thereby reducing joint pain and swelling and promoting joint function recovery [9–11, 18]. To the best of our knowledge, no study has compared the efficacies of intravenous administration and intra-articular injection of TXA in reducing postoperative hemarthrosis after ACLR. By comparing the drain output volume, pain, knee swelling, hemarthrosis and clinical functional score of IV administration, IA injection and no TXA, this study aimed to compare the effects of intravenous and intra-articular administration of TXA in improving early-phase outcomes after ACLR.
Intravenous administration of TXA can reduce the amount of drainage blood and postoperative hemarthrosis after ACLR without side effects [9, 10, 18]. In this study, it was found that intravenous administration of TXA could reduce postoperative drainage volume and hemarthrosis following ACLR and alleviate pain and knee swelling, similar to the results of the previous study [9, 10, 18]. TXA may penetrate large joints efficiently after IV administration [9, 19]. TXA was shown to exert its beneficial effects not only by reducing blood loss but also through its anti-inflammatory effects, which might improve analgesia after surgery [20]. This might explain the significantly lowered VAS score in patients who received IV-administered TXA. However, we found that IV administration of TXA did not significantly improve the Lysholm score at 4 weeks. Hetsroni [18] reported that compared to no use of TXA, IV administration of TXA did not improve the Lysholm score at 3 months in patients having ACLR, but Karaaslan et al. [10] found a significant difference in the Lysholm score between IV administration and no use of TXA 2 and 4 weeks postoperatively. The differences in the comparisons of Lysholm scores might be attributed to differences in TXA dose and frequency in different studies. Because the mean duration of the effect of TXA is approximately 3 hours, some studies suggested that a second dose should be administered to extend the effect over the first 6 hours, when most bleeding occurs [21, 22]. Our study and Hetsroni’s study [18] only gave intravenously administered TXA before tourniquet release, which might not be sufficient to maximize the positive physiological effects of TXA; however, 10 mg/kg of intravenous TXA was given before surgery and an intravenous infusion of 10 mg/kg/h was continued for 3 hours after the operation in Karaaslan’s study [10]. The regimen for intravenous administration of TXA requires further investigation.
In this study, we found that intra-articular injection of TXA could also significantly reduce drainage blood volume and postoperative hemarthrosis and relieve pain and knee swelling. Intra-articular injection of TXA can be quickly absorbed locally; the physiological half-life of TXA in the joint cavity is approximately 3 hours [23], thus local hemostasis can be achieved. To date, there has been only one study on intra-articular injection of TXA to reduce intra-articular hemarthrosis after ACLR [11], and the results of that study were similar to ours. The confusion of intra-articular injection of TXA after ACLR was that it was unclear whether TXA could harm the knee environment, particularly by potentially causing apoptosis of chondrocytes and tenocytes. Parker et al. [24] showed that TXA (with concentrations up to 40 mg/mL) had no effect on the glycosaminoglycan content of human articular chondrocyte hydrogels after 6 hours of exposure. However, some studies have shown that a higher concentration of TXA might have a detrimental effect on animal or human chondrocytes in vitro [24, 25]. It is worth noting that a post-arthroscopic knee is filled with some irrigation fluid and hemarthrosis, which might further lower the true concentration of TXA. The optimal dosage of intra-articular TXA still needs to be clarified in the future.
We found that there were no significant differences between intravenous administration and intra-articular injection of TXA in reducing postoperative blood drainage and hemarthrosis, alleviating pain and knee swelling, and improving knee function. Similarly, the comparative efficacies of IV administration and IA injection for reducing blood loss during TKA are still controversial. Some studies reported that compared to IV administration, IA injection of TXA seemed to be more effective in terms of reducing blood loss and transfusion frequency [26–28]. Another study reported that IV administration seemed to be more effective than IA injection, with a transfusion risk difference of 30% [19].In addition, some researchers concluded that there was no statistically significant difference in blood loss and transfusion rates between IA and IV use in TKA [29, 30]. Most likely, either IA administration or IV injection had its own advantage. For example, Sarzaeem et al. [31] reported that IA injection of TXA was more effective at decreasing postoperative drainage after TKA, but IV administration of TXA seemed to reduce the number of transfused units and the magnitude of the drop in hemoglobin more effectively. The argument for intravenous administration of TXA was that only a small portion of intravenously administered TXA reached the target surgical site, whereas intra-articular application of TXA could supply a higher concentration. The argument for intra-articular administration of TXA is the problem of penitential toxicity to chondrocytes. Therefore, it may be the surgeon’s preference as to what route of administration to use.
There were several limitations in this study. First, the follow-up period (4 weeks) was not long enough and there were not enough observation times points for the Lysholm scores. The first 3 months postoperatively is a significant period for preventing a delay in the rehabilitation program, so the exact long-term effect of TXA application on outcomes after ACLR could not be effectively analyzed in this study. Second, we only administered TXA intravenously 10 minutes before tourniquet release, which might not be sufficient to maximize the positive physiological effects of TXA. The regimen of intravenous administration of TXA requires further investigation. Third, in addition to intra-articular hemarthrosis, bleeding and hematoma at the tendon donor site were also of concern, and bleeding from the donor site was not self-limiting [32]. We only evaluated hemarthrosis with an intra-articular source, so the results might be biased.