Efficacy of tranexamic acid in improving visual clarity and operative time of arthroscopic rotator cuff repair: A systematic review and meta-analysis

Abstract

Objective:

The aim of this study was to examine if tranexamic acid (TXA) can assist in improving outcomes of arthroscopic rotator cuff repair (RCR).

Methods:

The databases of PubMed, Embase, Web of Science, CENTRAL, and Scopus were searched for all types of studies examining the efficacy of TXA for arthroscopic RCR. Twelve studies, 10 randomized controlled trials (RCTs), and 2 retrospective studies were considered eligible.

Results:

Meta-analysis of only 2 studies using a visual clarity grading system showed better visualization with the use of TXA. A similar difference was noted for studies using the visual analog scale. Operating time was not significantly different between the groups, but subgroup analysis of RCTs demonstrated reduced operating time with TXA. Meta-analysis showed no difference in 24-hour pain scores between TXA and control groups. Qualitative assessment of studies for blood loss showed no significant effect of TXA. No major complications were reported in any of the studies.

Conclusion:

This study has pooled evidence suggesting that TXA can improve visual clarity in arthroscopic RCR and may also result in a reduction in operating time. TXA does not seem to reduce blood loss or 24-hour postoperative pain scores.

Level of Evidence:

Level II, Therapeutic Study.

Highlights

• Rotator cuff tears are a common shoulder pathology, with arthroscopic rotator cuff repair (RCR) being an effective treatment option despite challenges such as bleeding and postoperative pain. This review aims to provide comprehensive evidence on the efficacy of tranexamic acid (TXA) in improving outcomes of arthroscopic RCR by reducing bleeding and enhancing procedural ease.

• The result showed that tranexamic acid (TXA) significantly improved visual clarity with a higher percentage of patients achieving grade 3 visibility. While meta-analysis showed no significant difference in overall operating time, subgroup analysis of RCTs demonstrated reduced operating times with TXA. Additionally, there was no significant difference in 24-hour pain scores.

• The findings suggest that TXA improves visual clarity and may reduce operating time during arthroscopic RCR, but it has no significant effect on blood loss, 24-hour pain scores, or complication rates, highlighting the need for further studies to address current limitations.

Introduction

Rotator cuff tear is a common shoulder pathology affecting about 13% of adults older than 50 years and about 50% of elderly aged >80 years.¹ The majority of the tears are small and asymptomatic while nearly a third of the lesions present with pain, restricted motion, and muscle weakness.² With partial and complete tears, there is a severe restriction of daily functioning, especially with overhead activities and pain localized to the deltoid region. Management of the tear depends on the severity and patient symptoms and can range from physical therapy to surgical intervention.³

Arthroscopic rotator cuff repair (RCR) has become an established treatment option for those requiring surgical intervention, with studies reporting good to excellent subjective outcomes and high levels of patient satisfaction.⁴ However, arthroscopic RCR does require soft tissue retraction and bone preparation, which can cause significant bleeding and postoperative pain. Excessive bleeding can potentially obstruct the surgical field, increasing operating time and the difficulty level of the surgery.⁵ Several methods have been reported in the literature to control bleeding like the use of epinephrine-based irrigation, electrocautery, hypotensive anesthesia, and pressure-controlled irrigation pumps.^6-9 However, in recent times there has been a spur of studies using tranexamic acid (TXA) to improve outcomes in arthroscopic surgeries.

TXA, a synthetic derivative of lysine, acts as an antifibrinolytic agent by blocking the action of plasminogen. Fibrin clots formed during the surgical procedure are thereby preserved, reducing bleeding and hematoma formation.¹⁰ The drug has been used for hip and knee arthroplasty and knee arthroscopic surgeries to reduce bleeding and transfusion requirements. It has been hypothesized that its use in arthroscopic RCR would also improve outcomes, thereby enhancing the ease of the procedure.^11,12 Over the past few years, several studies.^13-15 have been conducted examining the efficacy of TXA for arthroscopic RCR. Similarly, a few meta-analysis studies^16,17 have also been published, but these have not included all literature published to date. Therefore, the current review was conducted to provide comprehensive evidence on the effect of TXA in improving outcomes of arthroscopic RCR.

Material and methods

Search source and strategy

The review was registered on PROSPERO (CRD42023435709). A systematic search of the literature was done up to July 20, 2023, by 2 reviewers separately. A second search was rerun on May 27, 2024, to update the previous search. The databases examined were: PubMed, Embase, Web of Science, CENTRAL, and Scopus. Google Scholar was also searched for gray literature.

The inclusion of studies was based on the following PICOS criteria:

Population: Adult patients undergoing arthroscopic RCR.

Intervention: Use of TXA via any route.

Comparison: Placebo or no TXA.

Outcome: visual clarity, operating time, pain scores, blood loss, or complications.

Study type: Randomized controlled trials (RCTs) or retrospective studies.

Exclusion criteria were: (1) Not specifically on arthroscopic RCR or not reporting separate data for the same; (2) editorials, thesis, and non-peer-reviewed studies; and (3) duplicate studies.

The search was based on the following keywords: “rotator cuff”; “shoulder”; “arthroscopy”; and “tranexamic acid”. Different search strings were generated using “AND.” The search strings were similar across databases. Further details are mentioned in Supplementary Table 1.

Supplementary Table 1.

Search strategy

Query	Search Details
(rotator cuff) AND (tranexamic acid)	(“rotator cuff”[MeSH Terms] OR (“rotator”[All Fields] AND “cuff”[All Fields]) OR “rotator cuff”[All Fields]) AND (“tranexamic acid”[Supplementary Concept] OR “tranexamic acid”[All Fields] OR “tranexamic acid”[MeSH Terms] OR (“tranexamic”[All Fields] AND “acid”[All Fields]))
(tranexamic acid) AND (arthroscopy)	(“tranexamic acid”[Supplementary Concept] OR “tranexamic acid”[All Fields] OR “tranexamic acid”[MeSH Terms] OR (“tranexamic”[All Fields] AND “acid”[All Fields])) AND (“arthroscopy”[MeSH Terms] OR “arthroscopy”[All Fields] OR “arthroscopies”[All Fields])
(shoulder) AND (tranexamic acid)	(“shoulder”[MeSH Terms] OR “shoulder”[All Fields] OR “shoulders”[All Fields] OR “shoulder s”[All Fields]) AND (“tranexamic acid”[Supplementary Concept] OR “tranexamic acid”[All Fields] OR “tranexamic acid”[MeSH Terms] OR (“tranexamic”[All Fields] AND “acid”[All Fields]))

Study selection

Two reviewers examined all the search results independently. First, the retrieved data was congregated and deduplicated electronically. The titles and abstracts of all articles were screened to identify relevant studies. Non-relevant articles were excluded and the remaining underwent full-text analysis. The reviewers carefully screened these studies based on the following criteria for further inclusion. Any disagreements were solved by consensus. We also examined the reference lists of the included studies for any other missed articles.

Extracted data and outcomes

Two reviewers were independently involved in data extraction. A pre-formatted table was generated before beginning the review. Details sought were the author’s name, year of publication, study type and location, method, and dose of TXA administration, sample size, age and gender details, patient position, anesthesia used, analgesic protocol, and outcomes. Study details were then cross-matched and any discrepancies were resolved in discussion with the third author.

Risk of bias analysis

RCTs were evaluated using The Cochrane Collaboration risk of bias-2 tool.¹⁸ Studies were marked as low risk, high risk, or some concerns for each domain of the assessment tool. The different domains of the tool included the randomization process, deviation from intended intervention, missing outcome data, measurement of outcomes, selection of reported results, and overall risk of bias.

Non-RCTs were judged using the Newcastle-Ottawa Scale (NOS).¹⁹ The NOS has three domains: representativeness of the study cohort, comparability, and measurement of outcomes. Points are given based on the preformatted questions.

Statistical analysis

The review was conducted as per PRIMA guidelines.²⁰ Statistical analysis was done on “Review Manager” (RevMan, version 5.3; Nordic Cochrane Centre (Cochrane Collaboration), Copenhagen, Denmark; 2014). Data on continuous variables were extracted in the form of mean and standard deviation (SD). If unavailable, it was calculated based on available data (median, range) using the methods of Wan et al.²¹ Data were then combined to generate mean difference (MD) with 95% confidence intervals (CI).

All results were presented in the form of a forest plot. The meta-analysis was conducted in a random-effects model. Where possible, a subgroup analysis was done based on study type. In case studies that did not report outcomes using the same common scale, a descriptive analysis was done. Due to a low number of studies, funnel plots were not generated. The I² statistic was the tool to determine inter-study heterogeneity. I² <50% meant low, and >50% meant substantial heterogeneity.

Results

Search results

Results generated during the search strategy are shown in Figure 1. 535 articles were initially retrieved. Duplicates were excluded, leaving 224 records for further analysis. Seventeen of them were found suitable for full-text analysis of which 12 made it to the final review.^{13,14,29,30,15,22-28}

Figure 1.

Study flowchart.

Out of the 12 studies, 10 were RCTs, while 2 were retrospective studies (Table 1). All of them were published in the past four years and were from the countries of China, Turkey, Japan, Australia, and the United States. Seven studies used the intravenous (IV) route, 3 used intra-articular (IA) injections of TXA, 1 used periarticular injections while 1 study compared IV, IA, and combination of IV and IA with control. Amongst the studies using the IA route, 2 used TXA for intra-operative irrigation diluted in normal saline while one study injected TXA preoperatively and another postoperatively into the joint. For studies using the IV route, the drug was administered preoperatively in all studies. The most common dosage was 1 g. The number of patients in the study group varied from 32 to 83. Most studies used general anesthesia for the surgical procedure. Three studies also used inter-scalene plexus block in addition to general anesthesia. The beach chair or the lateral decubitus position was used by the studies for RCR. The postoperative analgesic protocol was not uniformly reported by the included studies.

Table 1.

Details of included studies

Study	Study type	Location	Method and dose of TXA administration	Groups	Sample size	Male gender	Age (years)	BMI (kg/m2)	Anesthesia	Position	Postoperative analgesics	Complications
Bildik 202326	RCT	Turkey	IA; 250 mg in 3L normal saline for irrigation	TXA Control	32 31	8 9	56.5 57.8	NR	GA	Beach chair	Acetaminophen 500g IV every 8 hourly, Ketorolac IM 24 hourly	None
Ersin 202013	RCT	Turkey	Preoperative 20 mins before surgery; IV route; 10mg/kg	TXA Control	32 28	15 11	49.6 53.1	28.1 28.6	GA	Beach chair	NR	NR
Gao 202015	RCT	China	IA in shoulder joint and subacromial space; 1g	TXA Control	30 30	6 5	62.3 63.4	NR	GA	Lateral decubitus	NR	Subcutaneous ecchymosis [6 in TXA and 2 in control]
Kawaguchi 202328	R	Japan	Preoperative after induction; IV route; 1g	TXA Control	64 65	38 41	64 64.9	24.2 24.2	GA	Beach chair	NR	None
Liu 202025	RCT	China	Preoperative 10 minutes before surgery; IV route; 1g	TXA Control	37 35	19 17	58.9 60.2	26.1 27.1	GA with ISPB	Lateral decubitus	Tramadol/ acetaminophen 37.5 mg/325 mg 4 times daily, morphine 4 mg SC, or ketorolac 30 mg IM if necessary	None
Mackenzie 202227	RCT	Australia	Preoperative before induction; IV route; 2 g	TXA Control	47 42	34 22	58 58	NR	GA with ISPB	Beach chair or lateral decubitus	NR	Frozen shoulder ecchymosis [1 in TXA and 5 in control]
Nicholson 202214	RCT	Unite States	Preoperative before induction; IV route; 1 g	TXA Control	50 50	39 29	59.7 59.2	20.9 30.3	ISPB	Beach chair	NR	NR
Shin 202424	RCT	Korea	Preoperative before induction; IV route; 1 g	TXA Control	32 31	11 14	64 64	24.9 25.6	ISPB	Lateral decubitus	NR	None
Takahashi 202329	RCT	Japan	Preoperative 10 mins before surgery; IV route; 1 g	TXA Control	33 33	24 19	61.6 61.6	NR	GA	Beach chair	Acetaminophen 1g IV every 6 hourly for 24 hours	NR
Takahashi-1 202323	RCT	Japan	Postoperative periarticular injection 1 g	TXA Control	34 36	15 20	61.9 61.2	NR	GA	Beach chair	Acetaminophen 1g IV every 6 hourly for 24 hours	NR
Zhu 202330	R	China	IA; after wound suturing; 1 g	TXA Control	83 79	37 25	60.2 60.3	23.8 23.8	GA with ISPB	Lateral decubitus	Fumiprofen 50mg IV 12 hourly	None
Wang 202322	RCT	China	IV group: 1 g injected preoperative 10 mins before surgery IA group: 0.42 mg in 1 L normal saline for irrigation IV and IA group: received both	TXA-IV TXA-IA TXA-both control	35 32 34 33	13 11 13 12	54.3 55.6 52.4 50.7	24.9 25 24.9 25.5	GA	Lateral decubitus	NR	NR

GA, general anesthesia;IA, intra-articular; IM, intramuscular; ISPB, interscalene plane block; IV, intravenous; NR, not reported; R, retrospective; RCT, randomized controlled trial; TXA, tranexamic acid.

Visual clarity

Visual clarity was assessed using either the visual analog scale (VAS) or a three-point grading system in the included studies. In the three-point grading system, grades 1, 2, and 3 represented poor, fair, and good visibility, respectively. In a meta-analysis of 2 studies using this system, the percentage of patients with grade 3 visibility was significantly higher in the TXA group as compared to the control group (MD: 9.10 95% CI: 4.0.5, 14.15 I² = 0%). The percentage of patients with grade 2 visibility was significantly lower in the TXA group (MD: −6.45 95% CI: −11.26, −1.63 I² = 0%). However, there was no significant difference in the percentage of patients with grade 1 visibility (MD: −2.60 95% CI: −6.32, 1.12 I² = 0%) (Figure 2). Bildik et al²⁶ also reported on visual clarity but using a 5-point scale wherein grade 1 was no disruption of the field due to bleeding and grade 5 was extreme disruption requiring open surgery. In their study, the percentage of patients with grade 1 clarity was significantly higher in the TXA group. Shin et al²⁴ also reported visual clarity on a 3-point scale where grade 1 was no or minimal bleeding and grade 3 was discontinuation of the procedure due to major bleeding even after coagulation. The authors found the TXA resulted in better outcomes in patients undergoing stage I intra-articular soft-tissue procedures. However, no difference was noted between TXA and control groups for patients undergoing acromioplasty, bursectomy, and greater tuberoplasty.

Figure 2.

Meta-analysis of visual clarity based on grading system between TXA and control groups.

Four studies reported data using the VAS. One study did not report SD values leaving three studies for the meta-analysis. Wang et al²² included three study groups (IA, IV, and IA plus IV) and all three were pooled separately. Pooled analysis showed significantly better VAS scores for visual clarity in the TXA group as compared to the control group (MD: 0.28 95% CI: 0.12, 0.43 I²=83%) (Figure 3). Kawaguchi et al²⁸ in their retrospective study noted significantly better visual clarity with the use of TXA as compared to their control group.

Figure 3.

Meta-analysis of visual clarity based on VAS scores between TXA and control groups.

Operating time

Eight studies reported data on operating time. Meta-analysis showed no significant difference in operating time with or without TXA (MD: −6.89 95% CI: −14.37, 0.58 I² = 85%) (Figure 4). The difference was significant for RCTs (MD: −8.50 95% CI: −14.46, −2.54 I² = 61%) but not for non-RCTs (MD: −4.92 95% CI: −31.08, 21.25 I² = 0%).

Figure 4.

Meta-analysis of operating time between TXA and control groups.

Pain

Meta-analysis of five studies showed no difference in the pain scores at 24 hours between TXA and control groups (MD: −0.36 95% CI: −0.83, 0.11 I² = 59%) (Figure 5). Zhu et al³⁰ reported only the number of patients with different VAS scores and hence the data was not included in the meta-analysis. They reported a significantly higher number of patients with lower VAS scores in the TXA group as compared to the control group. Similarly, Bildik et al²⁶ did not present SD values of pain scores and reported significantly lower pain in the TXA group.

Figure 5.

Meta-analysis of pain scores between TXA and control groups.

Blood loss

There was much variation in the included studies for the method of estimation of blood loss and the presentation of data which precluded a meta-analysis. The details are presented in Table 2. All except for the study of Zhu et al³⁰ noted no difference in blood loss between TXA and control groups.

Table 2.

Bleeding outcomes reported by the included studies

Studies	Measurement	Result
Liu 202025	Intra-operative blood loss by concentration of hemoglobin in washed irrigation fluid	No significant difference in TXA and control groups
	Change in serum hemoglobin levels	No significant difference in TXA and control groups
Takahashi 202329	Intra-operative blood loss by gauze visual analog scale	No significant difference in TXA and control groups
Gao 202015	Difference in hemoglobin at postoperative day 1	No significant difference in TXA and control groups
Kawaguchi 202328	Change in hemoglobin at postoperative day 1 and 7	No significant difference at day 1 but significantly higher hemoglobin levels in TXA group at day 7
	Total blood loss estimated by circulating blood volume calculated using the Nadler’s formula	No significant difference in TXA and control groups
Zhu 202330	Change in hematocrit levels	Significantly lower blood loss in TXA group

TXA, tranexamic acid.

Complications

Majority studies reported no complications with the use of TXA (Table 1). Gao et al¹⁵ reported cases of subcutaneous ecchymosis while Mackenzie et al²⁷ reported cases of frozen shoulder in both TXA and control groups.

Risk of bias

Table 3 demonstrates the risk of bias in the studies based on the reviewer’s judgment. Amongst RCTs, four were found to be high quality with an overall low risk of bias. Two studies had some concerns while another 4 has a high risk of bias. For non-RCTs, the NOS score was either 7 or 6. Both of the retrospective studies did not score any points for comparability of the study groups.

Table 3.

Risk of bias analysis

RCTs
Study	Randomization process	Deviation from intended intervention	Missing outcome data	Measurement of outcomes	Selection of reported result	Overall risk of bias
Liu 202025	Some concerns	Low risk	Low risk	Some concerns	Low risk	High risk
Ersin 202013	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Gao 202015	Low risk	Some concerns	Low risk	Some concerns	Low risk	High risk
Takahashi 202329	Some concerns	Low risk	Low risk	Some concerns	Low risk	High risk
Takahashi-1 202323	Some concerns	Low risk	Low risk	Some concerns	Low risk	High risk
Mackenzie 202227	Low risk	Low risk	Low risk	Some concerns	Low risk	Some concerns
Nicholson 202214	Low risk	Low risk	Low risk	Some concerns	Low risk	Some concerns
Shin 202424	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Bildik 202326	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Wang 202322	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Non-RCTs
Study	Selection of cohort	Comparability	Outcome assessment			Final score
Kawaguchi 202328	****	-	***			7
Zhu 202330	***	-	***			6

RCTs, randomized controlled trials.

Discussion

Overall the findings of this comprehensive review including all possible studies in the literature to date, indicate that TXA may improve visual clarity during arthroscopic RCR. Additionally, there may be a tendency for reduced operating time with the use of TXA. Also, there seems to be no effect of TXA on blood loss, 24-hour pain scores, or complication rates.

TXA is a popular antifibrinolytic agent which has long been used for short-term management of bleeding in several conditions like menorrhagia, gastrointestinal bleeds, epistaxis, hemoptysis, bleeding after dental extractions, post-partum hemorrhage, etc.³¹ Given its efficacy, the use of TXA has been quite popular in several surgical domains including orthopedics. Fillingham et al³² in a network meta-analysis of 67 studies have demonstrated that TXA decreases blood loss and risk of transfusion in total knee arthroplasty. Their study also showed that all formulations (oral, IV, topical) of TXA were superior to placebo and higher dosage did not translate into better outcomes. Another review of 34 publications has shown similar outcomes in patients undergoing total hip arthroplasty.³³ Pecold et al³⁴ in a review of 10 studies have also demonstrated a statistically significant reduction in blood loss and drain output with the use of TXA in shoulder arthroplasty. In comparison to open surgery, arthroscopic interventions have limited access and adequate visualization is the key for successful outcomes.⁵ A significant bleed during the procedure can obscure the field and may lead to conversion into open surgery. A recent review by Goldstein et al³⁵ have examined the efficacy of TXA in arthroscopic procedures. Combining data from seven RCTs predominantly on knee arthroscopy (just 1 study on shoulder arthroscopy), the authors concluded that TXA improved visual clarity while reducing drainage output, the incidence of hemarthrosis, and the need for joint aspirations. There was no increase in the risk of complications or reduction in operating time.

Unlike arthroscopy of the knee, where a tourniquet can be used to control bleeding and improve visual clarity, shoulder arthroscopy mainly relies on blood pressure control, volume of irrigation, and plasma radiofrequency hemostasis.³⁶ Traditionally, epinephrine diluted irrigation fluids have been used but the drug has a risk of rare but fatal adverse events like arrhythmias and cardiopulmonary arrest.^36,37 In this context, TXA can be an alternative agent to improve visual clarity. We hereby reviewed twelve studies examining the efficacy of TXA in improving visual clarity, operating time, and pain scores for arthroscopic RCR. In one of the earliest studies, Ersin et al¹³ conducted an RCT on the use of IV TXA administered 20 minutes preoperatively in patients undergoing arthroscopic RCR. The authors noted that visual clarity was significantly better in the TXA group and TXA was associated with reduction in the amount of irrigation solution needed. Liu et al²⁷ also conducted an RCT to examine the effects of IV TXA injected 10 minutes before surgery and found that TXA could be used to improve visual clarity, reduce pain scores, and decrease analgesic consumption in the early postoperative period after arthroscopic RCR. Similar improvement in visual clarity has been noted with the use of IV TXA in the RCT of Takahashi et al²² but without any improvement in swelling, pain scores, blood loss and operating time. Shin et al²⁶ in their RCT noted better visual clarity with the use of TXA but only for intra-articular soft-tissue procedures. No such effect was noted during acromioplasty, bursectomy, and greater tuberoplasty. Nicholson et al¹⁴ randomized 100 RCR patients to IV TXA and control group and found that use of TXA did not improve visual clarity and early pain scores nor did it improve the surgeons ability to maintain lower pump pressure during arthroscopic RCR. On the other hand, Kawaguchi et al³⁰ in a retrospective study using IV TXA noted a significant improvement in visual clarity, reduced operating time, and reduced blood loss up to the postoperative day 7 with the use of the drug. Mackenzie et al²⁹ conducted an RCT on IV TXA but used a dose of 2g and assessed only pain scores. The authors noted that TXA did not improve pain scores after RCR but resulted in greater range of motion at 6 months. Takahashi et al²⁵ examined the efficacy of periarticular injection of TXA on pain scores and found no significant impact of TXA on pain reduction after surgery. Gao et al¹⁵ in their RCT injected TXA in the shoulder joint and subacromial space and showed that TXA could reduce early swelling but had no effect on late swelling or blood loss. Zhu et al²³ in their retrospective study also studied the effect of TXA injected in the joint but after incision closure and found that TXA could reduce total blood loss and early postoperative pain. In an RCT, Bildik et al²⁸ examined the effects of TXA as an irrigation agent during the arthroscopic procedure only to find that use of TXA led to superior visual clarity, shortened operating time, and better pain relief at 8 and 24 hours after surgery. Lastly, Wang et al²⁴ conducted a four-arm RCT and compared the efficacy of IV, IA, and IV plus IA TXA with control in patients undergoing arthroscopic RCR. The authors found that both systemic and topical TXA were effective in improving visual clarity, but the combination of the two was more effective.

After collating the results of all published studies, our review demonstrated that despite differences in the scoring systems used by the studies, there seems to be evidence of improved visual clarity with the use of TXA. Combined analysis of two studies using the grading system showed better visualization with TXA. Likewise, studies using the VAS scale also showed similar results. Qualitative analysis of studies^26,28 not included in the meta-analysis also showed better visual clarity with TXA. A major drawback of assessing visual clarity is the subjective nature of the outcome and the variability in the methodology and timing of its measurement by the included studies. In one study,¹⁴ it was marked by the surgeons immediately after surgery, another study²⁵ examined visual clarity during the procedure after every 15 minutes intervals while in one study¹³ the operating surgeon and a blinded surgeon rated visual clarity using videos of the operation. Such marked differences combined with a disparity in route and dosage of TXA used prohibit robust conclusions on the efficacy of TXA in improving visual clarity in arthroscopic RCR.

Similarly, there was much variation in the method of assessment of blood loss among the studies, which precluded a meta-analysis. Unlike literature on arthroplasty and knee arthroscopy wherein TXA has significantly reduced bleeding,^11,32,35 the studies in the current review failed to demonstrate any significant effect on blood loss by TXA during arthroscopic RCR. One probable reason could be limited blood loss noted in arthroscopic RCR compared to other procedures and the difference may have been underestimated owing to the limited sample size of the included studies. A corollary of improved visual clarity due to less intraarticular bleeding can be reduced operating time. However, our meta-analysis also failed to show any significant difference in operating times between TXA and control groups. Based on the 95% CI of the effect size, there was a tendency to reduce operating time with TXA but the MD was just about 7 minutes, which may not have any clinical significance. Nevertheless, meta-analysis of only RCTs did demonstrate a significant reduction of operating time by a mean of 8.5 minutes. Given the variable patient population, surgeon experience, and routes of administration of TXA in the included RCTs, further investigations are needed to firmly establish the role of TXA in reducing operating time.

Hemarthrosis of the joint after surgery can increase postoperative pain and restrict the range of motion.³⁸ In knee arthroscopic procedures, TXA administration has been shown to improve functional outcomes and reduce pain scores postoperatively.³⁹ However, a limited meta-analysis of five studies in this review failed to demonstrate a significant effect on pain scores after arthroscopic RCR probably as an offshoot to no major difference in bleeding between the two groups. Importantly, there was no major adverse event associated with TXA use in any of the included studies. Since TXA promotes coagulation, there is always a risk of thromboembolic complications, which can be catastrophic, especially in patients with previous comorbidities.¹¹ Nevertheless, a large meta-analysis of 9067 patients undergoing lower limb surgeries has shown that TXA is not associated with an increased risk of thromboembolism when administered via any route.⁴⁰ Therefore, combined with the current evidence on arthroscopic RCR, TXA may be considered safe for such procedures.

The dose and route of administration of TXA have been a topic of controversy in the orthopedic literature. In the current review too, IV, IA, and periarticular injections of TXA were used with different dosages. Furthermore, a few studies also used TXA for IA irrigation. IA injections have been used to achieve higher concentrations of TXA at the surgical site without increasing the risk of adverse events.¹⁵ While TXA administered via the IV route can also reach the joint, the limitation is its short half-life with effects being maintained only for 4-6 hours.³⁰ Previous studies have shown that route of administration of TXA does not impact outcomes in arthroplasty procedures.^32,33 However, the literature is deficient for arthroscopic RCR and there is a need for further studies elucidating the impact of different routes of TXA on patient outcomes.

This meta-analysis has some limitations. Despite being an all-encompassing and updated review, we could include only twelve studies. The limited sample size of studies was also a major hindrance in generating high-quality evidence. Also, the quality of included studies was not high with several trials marked with bias in measurement of outcomes. Given the subjective nature of various outcomes, adequate blinding of patients and outcome assessors is extremely important. Two of the included studies were retrospective and are prone to selection bias. Furthermore, there was high heterogeneity in the method of TXA administration which could have skewed outcomes. Given the limited data available, we were unable to conduct a subgroup analysis for the route of administration. Lastly, data was not coherently reported by the studies with variations in the method of assessment and data presentation. Lack of reporting of data as median [interquartile range] or mean and SD resulted in many studies being excluded from quantitative analyses.

Pooled evidence suggests that TXA can improve visual clarity in arthroscopic RCR and may also lead to reduction in operating time. TXA does not seem to reduce blood loss or 24-hour postoperative pain scores. Scarcity of data, variability in the measurement of outcomes, and differences in the route of TXA administration are major limitations that need to be addressed by future studies.

Funding Statement

The authors declared that this study has received no financial support.

Data availability statement:

The data that support the findings of this study are available from the corresponding author upon reasonable request.