Tranexamic acid (TXA) is widely used across multiple surgical specialties, including cardiac, neurosurgical, and orthopedic procedures. It is most frequently administered intravenously in the preoperative setting, although the topical and oral routes have been explored and produced comparable outcomes. TXA acts as an antifibrinolytic agent, stabilizing fibrin clots to reduce perioperative bleeding and transfusion requirements [1,2].

In orthopedic surgery, TXA has been shown to reduce blood loss and transfusion rates without increasing the risk of venous thromboembolism, particularly during total hip and knee arthroplasty [3]. Intravenous administration remains the most common and effective route, given its rapid systemic distribution and ability to reach large joints efficiently [2]. Topical application has demonstrated efficacy similar to intravenous delivery in terms of blood loss and transfusion rates [4,5]. Oral administration has also been reported to provide comparable safety, with additional benefits of reduced transfusion rates, cost-effectiveness, and ease of administration for total hip and knee replacement, as well as for intertrochanteric fracture surgery [6,7].

In shoulder surgery, intravenous TXA has been associated with reduced perioperative blood loss, lower postoperative pain in the early recovery period, and decreased hematoma formation [8]. A meta-analysis of patients undergoing total shoulder arthroplasty, reverse shoulder arthroplasty, or arthroscopic rotator cuff repair demonstrated that TXA reduced blood loss and might have contributed to lower postoperative pain and shorter operation times [9]. Another meta-analysis confirmed its safety profile, showing no increased risk of complications or thromboembolic events; however, it found that TXA did not reduce intraoperative bleeding sufficiently to improve visualization during arthroscopic rotator cuff repair [10]. Those findings are clinically relevant because several factors—such as low perioperative hemoglobin, procedures for periprosthetic joint infection, and fracture-related surgeries—have been linked to increased risk of transfusion during shoulder surgery [11].

Several systematic reviews and meta-analyses have specifically examined the role of TXA in arthroscopically treated rotator cuff tears [10,12-14]. The most recent systematic review on this topic was conducted by Jain et al. [15]. However, the interpretation of results across those studies is limited by methodological heterogeneity, particularly the lack of pre- and postoperative values for key clinical outcomes. This absence of standardized data complicates the assessment of TXA efficacy—whether administered intravenously or intra-articularly—and hinders reliable interpretation. Therefore, we conducted this systematic review to evaluate the efficacy of TXA in primary arthroscopic rotator cuff repair, with specific attention to operative field visualization, operation time, mean arterial pressure (MAP), hospital length of stay, postoperative pain and function, and complications including thromboembolic events.

This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting systematic reviews and meta-analyses [16]. This study did not involve human participants, and therefore ethical approval and consent to participate were not applicable.

Studies of the use of TXA in arthroscopic rotator cuff repair have yielded inconclusive results across multiple evaluated outcomes. Visual clarity was the primary endpoint in most studies; however, evidence for the efficacy of TXA remains inconsistent, irrespective of intravenous or intra-articular administration. The secondary outcomes of patient-reported measures, operation duration, MAP, and hospital length of stay also failed to demonstrate significant benefits associated with TXA use. Even the potential effect of TXA on reducing intraoperative irrigation fluid volume remains uncertain. Most of the included studies compared TXA with placebo (saline solution), but one trial evaluated TXA against epinephrine [19].

Several meta-analyses have assessed the effect of TXA on visual clarity during arthroscopic procedures, and the results have been mixed. Malik et al. [31] and Hurley et al. [32] reported that TXA improves intraoperative visualization, whereas Zhao et al. [12] and Jain et al. [15] described only a potential benefit. In contrast, Sun et al. [10] and Alyousef et al. [13] observed no significant improvement, which is consistent with our findings. Closer examination of those studies highlights important limitations. In the meta-analysis by Malik et al. [31], data from certain studies (e.g., [20,23]) were incorrectly extracted, raising concerns about the validity of their conclusions. Hurley et al. [32] did not conduct a pooled analysis or provide a forest plot but instead offered a narrative synthesis that suggested improved visualization with TXA. Conversely, Sun et al. [10], Alyousef et al. [13], and Alzobi et al. [14] reported no benefit, findings that align with our results.

Our analysis focused on arthroscopic rotator cuff repair found no definitive benefit of TXA (intravenous or intra-articular) in improving visual clarity. We included eight studies for critical appraisal of this outcome, three more than the largest previously reported analysis. A significant challenge in synthesizing the available evidence is the considerable heterogeneity in the methods used to assess visual clarity. The reported scales ranged from 3- to 10-point systems, limiting comparability and hindering data pooling. One study used time-based assessments, such as calculating the proportion of operative time with optimal visualization [27], and another evaluated clarity across surgical stages [26]. Given that level of variability, the construction of forest plots and subsequent meta-analysis were not recommended. One study (Bildik et al. [20]) reported that intra-articular TXA administration produced better surgical field visualization than intravenous administration; the route of administration for TXA might influence its effects, and future studies comparing administration approaches should clarify that difference. The lack of standardized assessment methods might have either under- or over-estimated the true effect of TXA on surgical visualization. The implementation of a standardized surgical visual clarity evaluation could help to elucidate whether the use of TXA offers true clinical benefit for surgeons and patients.

The one RCT that compared TXA, epinephrine, and their combination in shoulder arthroscopy for various pathologies reported that TXA was less effective than epinephrine in improving visualization [33]. Those findings are consistent with the meta-analysis by Zhao et al. [12], which demonstrated that TXA reduced the operation time compared with saline but not compared with epinephrine, suggesting that TXA might not be a superior option for enhancing surgical field clarity.

From a biological mechanism point of view, TXA's limited visualization improvement could be due to non-hemostatic factors that require complementary techniques. TXA functions by inhibiting plasminogen activation to plasmin, reducing fibrin degradation and blood loss [34]. However, visual clarity depends on multiple factors, including irrigation fluid composition and pressure management [35] and surgical manipulation. One study reported that, although TXA reduces bleeding, epinephrine's vasoconstriction properties can more effectively manage intraoperative bleeding by reducing blood flow, improving visual clarity [19].

In our study, postoperative pain improved in both the TXA and control (saline) groups, with no statistically or clinically meaningful differences between interventions. Although patients receiving TXA demonstrated marginally lower VAS scores at 8 and 24 hours (0.5–0.7 points), that reduction is well below the established minimal clinically important difference (MCID) for postoperative pain after arthroscopic rotator cuff repair (>1.5 points). These findings indicate that, despite minor numerical differences, TXA does not provide a clinically relevant advantage in terms of patient-reported pain relief [36,37].

Previous studies have yielded conflicting results for this outcome. Whereas some meta-analyses suggest that TXA could shorten operation time and reduce postoperative shoulder pain, even within the first 24 hours [13,14,31,32], others have found no meaningful effect [9,10]. For instance, Alzobi et al. [14], reported only a modest reduction in pain, the clinical significance of which remained questionable. More importantly, substantial heterogeneity in study design, timing, and methods of pain assessment weakened the reliability of those pooled effects. MacKenzie et al. [24] evaluated pain at different postoperative time points, and Takahashi et al. [27] assessed pain across multiple contexts (at rest, activity, at night). In contrast, the meta-analysis by Hurley et al. [32] considered only resting pain, neglecting potentially relevant dimensions of patient experience. Moreover, the meta-analysis by Hurley et al. [32] incorporated data from studies with inconsistent protocols, including VAS scores obtained on day 0 and from patients who did not receive the allocated intervention (e.g., 24), further compromising interpretability. Similarly, Jiang et al. [22] compared TXA alone and in combination with dexamethasone against a control group and found no clear benefit of either treatment. Bayram et al. [19], who compared TXA with epinephrine, did not evaluate postoperative pain, limiting the scope of their findings. These methodological shortcomings underline the fragility of the current evidence base and highlight the need for more rigorously designed trials to clarify the analgesic role of TXA in arthroscopic rotator cuff repair.

By focusing exclusively on arthroscopic rotator cuff repair and using consistent pain assessment time points, our study avoids many of the methodological inconsistencies seen in prior research, offering a more targeted evaluation of TXA’s effect on postoperative pain. Even when statistical significance can be observed with the use of TXA in arthroscopic rotator cuff repair, the difference is likely clinically meaningless because the MCID was not reached.

Regarding functional outcomes, the pooled effect size revealed no significant difference in postoperative ASES scores between the TXA and control groups. The wide confidence intervals and not significant p-values reflect substantial uncertainty in the effect estimate, likely influenced by the small sample size and limited patient follow-up. Importantly, this endpoint has not been evaluated in prior meta-analyses due to the paucity of trials reporting functional scores, which emphasizes the limited evidence base that precludes any definitive conclusion about the functional impact of TXA in shoulder arthroscopy.

Most studies reported no significant differences in operation time, suggesting that TXA has no substantial effect on surgical duration except under specific conditions. However, Bildik et al. [20], observed a significant reduction of approximately 12 minutes in operation time with intra-articular administration of TXA. In contrast with intravenous administration, intra-articular TXA could exert localized hemostatic effects, reducing intraoperative bleeding and enhancing visualization, which could contribute to a more efficient surgical process. Nonetheless, differences related to the route of administration warrant further investigation because the surgical technique, surgeon experience, and institutional protocols could act as confounding factors. A more detailed sub-analysis comparing administration routes was not feasible in this study due to the heterogeneity of visualization assessment and the small number of studies that evaluated the intra-articular approach.

Two previous meta-analyses [13,32] reported a significant reduction in operation time with TXA use in arthroscopic rotator cuff repair. Both those analyses included the same five trials, which likely explains their identical findings. In contrast, our review incorporated eight studies—the same five plus three additional trials. Among them, only Bildik et al. [20] demonstrated a significant reduction in operation time with TXA. The remaining studies, including Bayram et al. [19], which compared TXA with epinephrine, found no meaningful difference in surgical duration between groups. Furthermore, a broader meta-analysis including various shoulder procedures (arthroscopic, open, and arthroplasty) reported reduced blood loss with TXA use [10], which could indirectly shorten operation time. However, that effect appears less consistent when analyses are limited to arthroscopic rotator cuff repair.

One of the major concerns during shoulder surgery performed in the beach chair position is the risk of cerebral hypoperfusion. Current recommendations advise maintaining systolic blood pressure above 90 mmHg and limiting reductions in systolic pressure and MAP to less than 20% from baseline to minimize that risk [38]. As noted in this study, there is no universally preferred patient position for shoulder arthroscopy; the choice is generally based on the surgeon’s preferences. The use of TXA has not been shown to affect MAP; all the studies included here reported values comparable to those in the control groups.

Several concerns are associated with the volume of fluid used in shoulder arthroscopy. These include hypothermia [39], fluid retention in the surrounding tissues (particularly when automated pump systems are used), a variable local inflammatory response [40], decreased hemoglobin levels, and alterations in serum sodium [41]. Although no standardized or recommended fluid volume has been established for shoulder arthroscopy, lower volumes are generally preferred to minimize those risks. Evidence indicating that TXA can significantly reduce fluid requirements remains inconclusive.

The use of TXA in shoulder surgery appears to be safe with respect to thromboembolic events [8]; no adverse events—general or thromboembolic—were reported across any of the studies we analyzed. This is consistent with the benefits of TXA established in other orthopedic procedures [42]. Specifically, in total shoulder arthroplasty, intravenous TXA has been associated with reduced perioperative blood loss and drainage, as well as decreased early postoperative pain [8]. In arthroscopic shoulder surgery, its use has shown promise in reducing hemarthrosis and early postoperative complications compared with controls [33].

Several limitations of this review must be acknowledged. Heterogeneity in outcome assessment, particularly for visual clarity, disallowed meaningful data pooling and meta-analysis in some cases. Functional outcomes were underreported and, where they were available, analysis was limited by small sample sizes and wide confidence intervals. The overall power of the included studies might have been insufficient to detect modest effects, particularly for secondary outcomes. Comparisons with epinephrine—a commonly used agent—were limited to a single study, restricting conclusions on the relative efficacy of TXA. Because epinephrine showed better visualization than TXA, it is necessary to conduct additional RCTs to determine the true superiority between them. Additional variability in TXA administration (e.g., dosage, route, and timing), surgical techniques, and perioperative protocols across studies might have introduced bias and reduced the generalizability of the findings. A limited comparison of functional scores was observed; only two studies included this evaluation, and they both had short follow-up times. Therefore, a long-term evaluation of large-scale studies with sufficient power is needed to determine whether TXA influences shoulder functionality. To overcome those limitations, we focused exclusively on arthroscopic rotator cuff repair, providing a more targeted and clinically relevant analysis than previous reviews that considered a broader range of shoulder procedures. We also included a greater number of studies than earlier meta-analyses, allowing a more comprehensive evaluation of TXA effects. Finally, we critically addressed methodological inconsistencies in prior research, such as inconsistent pain assessment and data extraction errors.

Current evidence is insufficient to support the routine use of TXA in arthroscopic rotator cuff repair, so it should be considered only in specific clinical scenarios. Across key outcomes—visual clarity, postoperative pain, operation time, functional recovery, MAP, and fluid use—TXA showed no significant advantage over the control. Although intra-articular TXA might offer localized effects, evidence about its effects on surgical efficiency and recovery remains inconclusive. Given its favorable safety profile, TXA might be a valuable option for specific high-risk patient populations (e.g., patients on anticoagulants or revision surgery) in which the risk of bleeding is a serious concern. Future studies should focus on determining the optimal dose, administration route, and efficacy of TXA in specific patient subgroups.