Our study revealed that the intraoperative topical administration of TXA significantly reduced perioperative blood loss and blood transfusion volumes, as well as postoperative medical complications, in elderly patients with femoral neck fractures who underwent hemiarthroplasty. These findings suggest that this simple and cost-efficient procedure is highly effective in elderly patients undergoing hemiarthroplasty for femoral neck fractures.
TXA has been widely used to reduce blood losses and transfusion requirements following hip arthroplasty, and has been shown to confer these benefits when established in IV, topical, and oral forms [22,23,24]. Several studies have demonstrated that blood transfusion results in a longer hospital stay and increased morbidity and mortality, and have identified it as an independent risk factor for periprosthetic joint infection [25,26,27]. Another study demonstrated that a restrictive transfusion policy leads to increased cardiovascular events and increased mortality rates [28]. However, transfusion, regardless of the amount of transfusion, is associated with an increased long-term mortality after hip fracture surgery [5]. Therefore, it is important to reduce perioperative blood loss and transfusion requirement after hip fracture surgery, especially in elderly patients with comorbidities. However, the current literature contains little information about the effects of TXA on surgical outcomes after arthroplasty in elderly patients with hip fracture.
Recent systematic reviews and meta-analyses have reported that the topical application of TXA to the joint during surgery might be effective [29,30,31]. Furthermore, this administration route was shown to reduce systemic effects, compared to oral or IV TXA administration, but was not found to increase the risk of thromboembolic events [31, 32]. Therefore, we conducted this case-control study to evaluate the efficacy and safety of topical TXA in terms of surgical outcomes after hemiarthroplasty in elderly patients with femoral neck fracture.
In our study, topical TXA significantly reduced perioperative blood loss, vacuum drainage, and rate and total amount of blood transfusion in our cohort, although it did not affect the change of Hb and Hct levels, the lengths of ICU and hospital stays or the rates of in-hospital and 1-year mortalities. In terms of blood loss, we measured total blood loss from operation to postoperative day 5 using the Gross formula (Mercuriali’s formula) based on the volume of transfused RBC and the change of hematocrit during the meanwhile and compared between the two groups. Accordingly, we believe that total blood loss estimated in our study was relatively accurate and that topical TXA injection reduced postoperative bleeding although there might be no difference in intraoperative bleeding between the two groups. Topical TXA injected into surrounding soft tissue, capsule, and muscles might reduce postoperative bleeding leaked out from these structures. Topical TXA significantly reduced the transfusion rate in the case group in spite of only small differences in the change of Hb and Hct levels between the two groups. We believe that small difference of Hb and Hct at postoperative day 1 and 5 between the two groups was caused by compensation by subsequent more transfusion due to more blood loss during early postoperative period in the control group.
Consistent with our findings, Tuttle et al. [33] reported that topical TXA reduced transfusion rates and costs and increased the frequency of hospital discharge to home rather than to a subacute nursing facility among patients undergoing primary hip and knee arthroplasty, but noted no significant difference in the length of hospital stay. The current study also revealed that transfusion rate was significantly lower in the study group than control group. However, the rate of transfusion in this study is relatively higher than other studies reporting 6 to 26.2% [34, 35]. In our hospital, anesthesiologists empirically tend to decide intraoperative transfusion considering patients’ comorbidities and conditions. Therefore, more elderly patients at high risk of complication due to comorbidities tended to receive intraoperative transfusion even at Hb > 8 g/dL. More intraoperative transfusions performed by anesthesiologists might increases total transfusion rate in our cohort. Also, some patients received postoperative transfusion at Hb > 8 g/dL according to the recommendation of specialists considering patients’ comorbidities and conditions, postoperatively. For these reasons, the transfusion rate in our study was relatively high compared to other studies. However, there was no significant difference in transfusion rate at Hb > 8 g/dL perioperatively between the two group. Similar portion of patients with these comorbidities and medical conditions in both groups would have shown similar rate of transfusion at Hb > 8 g/dL perioperatively between the two groups. Finally, these findings mean that more patients in the control group not receiving topical TXA injection received transfusion at Hb ≤8 g/dL due to more perioperative blood loss.
As noted, there have been no previous studies reporting on the effects of topical TXA, including postoperative complications and mortality, in fragile elderly patients. Our investigation revealed that topical TXA administration reduced the incidence of postoperative medical complications after hemiarthroplasty in these patients but had no significant effects on surgical complications and mortality. We therefore believe that reductions in postoperative blood loss and transfusion requirement mediated by topical TXA, directly or indirectly reduced postoperative medical complications in these fragile patients. It would be difficult to turn out that these medical complications were the result of an entirely increased total blood loss. However, the patients receiving more transfusion due to more perioperative blood loss would be delayed in ambulation and rehabilitation, and less active than patients not receiving postoperative transfusion. These conditions may have influenced the occurrence of medical complications such as cardiovascular, urologic and nephrologic problems, directly or indirectly.
Several authors have reported that the topical administration of TXA reduces blood loss and transfusion rates in patients undergoing primary hip and knee arthroplasty [32, 36, 37] and that the topical administration allows the maximum application of TXA directly to the surgical site while preventing potential systemic side effects. However, no consistent guidelines have been established regarding the dose and method of topical TXA administration. Regarding the determination of TXA dosage, Alshryda et al. performed a meta-analysis of 14 randomized controlled trials regarding the topical administration of TXA in total hip and knee arthroplasty and reported that the doses ranged from 250 to 3000 mg [31]. In another meta-analysis by Chen et al. [30], the doses of topical TXA during total hip arthroplasty varied from 0.5 to 5 g. In our study, we applied a relatively lower TXA dose of 1 g, given our concerns regarding the safety of this drug in elderly patients and less invasive nature of hemiarthroplasty relative to total hip arthroplasty, particularly as the effect of topical TXA is not dose-dependent [31, 38]. Regarding the topical application method, Konig et al. [32] bathed the joint in 20 mL of a TXA solution, while Yue et al. [22] applied gauze soaked in TXA solution to the acetabulum and femoral canal based on the method of Konig et al. [32]. We opted not to use the gauze-packing method because of concerns of surgical prolongation. Moreover, Kang et al. [18] administered a TXA solution into the joint through a drainage tube immediately after wound closure. However, this method might reduce the drug effect because TXA might have leaked from joint through the drain tube. Therefore, we directly injected TXA into the joint capsule and periarticular soft tissue.
Regarding strengths of this study, it was the first to evaluate the effects of topical TXA, including postoperative complications and mortality, in fragile elderly patients (≥ 70 years) undergoing bipolar hemiarthroplasty for femoral neck fracture. Both the study and control groups underwent procedures performed by the same surgeon via the same approach. Accordingly, topical TXA administration was the sole independent variable. Furthermore, the analysis was strengthened by propensity matching in terms of demographic data, ASA score, and time to operation between the two groups. Finally, our evaluation of the amount of total blood loss, which was based on the Hct levels and Gross formula, was more accurate than evaluations based on clinical calculation involving blood-soaked gauzes, suction bottles, and vacuum drains.
However, this study also had the following limitations. Despite the use of propensity score matching, this was a retrospective study with a small number of patients in each group. Furthermore, the incidence of thromboembolism was not assessed accurately, as only patients with clinical symptoms were subjected to diagnostic tests such as ultrasonography or 3-dimensionalCT-angiography.