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Effect of tranexamic acid in arthroscopic
anterior cruciate ligament repair:
A systematic review and meta-analysis
of randomised clinical trials
Tze Khiang Tan
1
, Ka Ting Ng
2
, Hui Jane Lim
3
and Ross Radic
4
Abstract
Purpose: Perioperative blood loss remains a major challenge to surgeons in anterior cruciate ligament reconstruction
(ACLR) surgery, despite of the introduction of minimally invasive approach. Tranexamic acid (TXA) is believed to reduce
blood loss, which may minimise the complication of postoperative haemarthrosis with insufficient evidence on its
effectiveness in ACLR. The primary aim of this study was to examine the effect of TXA on postoperative blood loss and
other secondary outcomes in patients undergoing arthroscopic ACLR surgery. Method: PUBMED, EMBASE, MEDLINE
and CENTRAL database were systematically searched from its inception until November 2020. All randomised clinical
trials (RCTs) comparing TXA (intravenous or intra-articular) versus placebo in the arthroscopic ACLR surgery were
included. Case series, case report and editorials were excluded. Results: Five RCTs comprising of a total of 580 patients
(291 in TXA group, 289 in control group) were included for qualitative and quantitative meta-analysis. In comparison to
placebo, TXA group was significantly associated with lower postoperative blood loss (mean difference (MD): 81.93 ml;
95% CI 141.80 to 22.05) and lower incidence of needing knee aspiration (odd ratio (OR): 0.19; 95% CI 0.08 to 0.44).
Patients who randomised to TXA were also reported to have better range of movement (MD: 2.86; 95% CI 0.54 to 5.18),
lower VAS Pain Score (MD: 1.39; 95% CI 2.54 to 0.25) and higher Lysholm Score (MD: 7.38; 95% CI 2.75 to 12.01).
Conclusion: In this meta-analysis, TXA reduced postoperative blood loss with lesser incidence of needing knee
aspiration along with better range of knee movement and Lysholm score in patients undergoing arthroscopic ACLR
surgery.
Keywords
anterior cruciate ligament repair, blood loss, meta-analysis, pain score, tranexamic acid
Date received: 18 January 2021; Received revised 25 April 2021; accepted: 26 April 2021
Introduction
The arthroscopic-guided anterior cruciate ligament
reconstruction surgery (ACLR) has replaced the approach
of open incision due to better anatomical visualisation and
minimal trauma impact on delicate structures surrounding
the knee.
1
As a result, arthroscopic approach offers better
recovery rate with shorter rehabilitation period and early
return to work.
1
Thus, the number of patients undergoing
ACLR surgery is on the rise every year.
2
Despite of its
minimally invasive technique, it still comes with complica-
tions, namely postoperative haemarthrosis and pain, which
1
Sir Charles Gairdner Hospital, Perth, WA, Australia
2
Department of Anaesthesiology, Faculty of Medicine, University of
Malaya, Kuala Lumpur, Malaysia
3
Altnagelvin Area Hospital, Londonderry, UK
4
Perth Orthopaedics and Sports Medicine Research Institute, West Perth,
WA, Australia
Corresponding author:
Tze Khiang Tan, Sir Charles Gairdner Hospital, Perth, Hospital Ave,
Nedlands WA 6009, Australia.
Email: khiang94@gmail.com
Journal of Orthopaedic Surgery
29(2) 1–9
ªThe Author(s) 2021
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DOI: 10.1177/23094990211017352
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Journal of
Or thopaedic
Surger
y
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Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
could delay the recovery and rehabilitation process.
3,4
Bahl
and colleagues reported that the duration of first 3 months
postoperatively is a critical period for rehabilitation and
recovery to restore full range of knee movement.
5
Two
common bleeding sources were identified mainly from
intra-articular femoral or tibial tunnels and harvested graft
sites.
6
Some surgeons advocate placing a drain at the sur-
gical site prior to skin closure but multiple randomised
controlled trials (RCTs) have proven this technique to
be ineffective in the reduction of haemarthrosis in ACLR
surgery.
6–9
Tranexamic acid (TXA) is a synthetic analogue of
lysine, which acts as a competitive inhibitor at the plasmi-
nogen lysine-binding site to reduce postoperative bleed-
ing.
10
It is believed that the use of TXA reduced
postoperative blood loss and incidence of severe haemar-
throsis in patients undergoing ACLR surgery.
11
Several
studies have also reported lower incidence of blood trans-
fusion in patients randomised to TXA in orthopaedic
surgery.
12–14
Furthermore, TXA has proven to be effective
in reducing blood loss in other surgeries, such as transplant
surgery, orthopaedic surgery and cardiac surgery.
14,15
However, the use of TXA comes with its fatal adverse
effect of thromboembolic events.
16
The administration of
TXA can either be given intravenously or direct intra-
articular injection. McCormack reported that the plasma
concentration of topical TXA was 90%lower than intrave-
nous TXA, which may minimise its adverse events.
17
A
recent meta-analysis and systematic review comprising of
71 RCTs with 7539 patients showed that topical TXA is
effective in reducing postoperative blood loss and inci-
dence of blood transfusion without any significant TXA’s
adverse events in patients undergoing any surgical proce-
dures.
18
Several recent RCTs investigating the use of intra-
venous or intra-articular TXA in arthroscopic ACLR
surgery were published with conflicting findings.
11,19–22
Thus, a systematic review and meta-analysis is warranted
to summarise the evidence use of TXA (intravenous or
intra-articular) in arthroscopic ACRL surgery before any
recommendation is made.
We hypothesised that the use of TXA reduced post-
operative blood loss in patients undergoing arthroscopic
ACLR surgery. The primary aim of this systematic review
and meta-analysis was to examine the effect of TXA on
postoperative blood loss in arthroscopic ACLR surgery.
Secondary aims were to investigate the effect of TXA on
pain score, Lysholm score, severity of haemarthrosis, range
of knee movement and incidence of needing for knee
aspiration.
Materials and methods
This systematic review and meta-analysis were conducted
according to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement stan-
dards.
23
The protocol was published on PROSPERO
(CRD42020219757) before the literature search was
conducted.
Search methods
Databases of OVID MEDLINE, OVID EMBASE,
CENTRAL and PUBMED were systematically searched
from their starting date until November 2020 for any RCTs
comparing TXA versus placebo in arthroscopic ACRL sur-
gery using autograft with or without meniscal surgeries.
Keywords utilised for the search included ‘Tranexamic
Acid [MeSH] OR Tranexamic Acid (All Text)’ and ‘Con-
trol Groups [MeSH] OR Control Group (All Text) OR
Placebo Group (All Text)’ and ‘Anterior Cruciate Liga-
ment Reconstruction [MeSH] OR Anterior Cruciate Liga-
ment (All Text) OR Anterior Cruciate Ligament
Reconstruction (All Text) OR Anterior Cruciate Ligament
Repair (All Text) OR Arthroscopic Anterior Cruciate Liga-
ment Reconstruction OR Orthopedics’. Any ongoing clin-
ical trials of the relevant topic were also searched on the
ClinicalTrials.gov.my. Thesearchapproachandsearch
strategy are outlined in the Online Supplementary Tables 1
and 2, respectively. Observational studies, review papers,
case series and case reports were excluded from this review
and no language restriction was applied. Patients less than
18 years old or those with coagulative disorder or anti-
coagulant therapy or thrombophilia were also excluded.
All references of relevant articles were manually checked
for any additional studies. Emails were sent to the relevant
authors to request for any unclear data or missing
information.
Based on the inclusion and exclusion criteria, the titles
and abstracts of articles were independently screened by
two authors (TKT and HJL). Any disagreement was
resolved by a third author (RR). Subsequently, full text
articles were screened by two authors (TKT and HJL) inde-
pendently. Any conflicts were resolved by a third author
(RR). The final included articles were discussed among all
the authors to reach a general consensus. Primary outcome
was postoperative blood loss (ml) in arthroscopic ACLR
surgery. Secondary outcomes included pain visual analo-
gue score (VAS), severity of haemarthrosis, range of knee
movement, incidence of needing for knee aspiration and
Lysholm score.
An online data extraction form was piloted prior to the
process of data extraction. Two authors (TKT and HJL)
independently extracted data from the included studies. A
third author (RR) cross-checked the accuracy of the
extracted data. Apart from the measured outcomes, other
data namely name of author, year of publication, mode of
administration TXA, total sample size and baseline demo-
graphic data were also extracted. Any values presented as
median with range or interquartile range or 95%confidence
interval (CI) were converted into mean +standard devia-
tion.
24
Any discrepancies encountered were resolved by
consulting a third author (RR).
2Journal of Orthopaedic Surgery 29(2)
The risk of bias assessment was conducted independently
by two authors (TKT and HJL) using the Cochrane Risk of
Bias Assessment tool.
25
The criteria of assessment included
selection bias, performance bias, detection bias, attrition
bias, reporting bias and other potential sources of bias.
26
For
all the domain of criteria, all the included RCTs were clas-
sified into low, unclear, and high risk of bias. Any disagree-
ment was resolved via a discussion with a third author (RR).
Data analysis
Review Manager 5.3 software was utilised for data analy-
sis. Mean difference (MD) was calculated as summary
measure for continuous outcomes while odd ratio (OR) was
calculated as the summary measure for dichotomous out-
comes with 95%confidence interval. p-value of <0.05 was
denoted as statistically significant difference for all the
reported outcomes. The I-square (I
2
) statistical test was
used to evaluate degree of heterogeneity across studies.
25
Value of I
2
less than 40%, 40–60%and more than 60%
were considered as low, moderate and substantial degree
of heterogeneity, respectively. Fixed-effect model was
used for all the measured outcomes. If substantial hetero-
geneity was observed, a random-effect model was utilised.
A subgroup analysis was performed based on different
route of TXA administration for all the reported outcomes
if adequate data was available.
Results
The PRISMA flow is displayed in the Figure 1. Searching
four databases (OVID MEDLINE, OVID EMBASE,
CENTRAL and PUBMED) identified 630 articles for
titles/abstracts screening after the removal of duplicates.
Applying inclusion and exclusion criteria, 15 articles were
included for full text screening. Among all, 10 studies were
excluded, which is showed in the Online Supplementary
Table 3. The final five included RCTs (a total sample size
of 580 patients) were included for qualitative and quanti-
tative analysis.
11,19–22
Searching of trial registry identified
two ongoing study and one completed study as shown in the
Online Supplementary Table 4.
Study characteristics
The publication dates of all the included studies ranged
from 2015 to 2020. Two RCTs adopted the route of intra-
articular injection and the remaining three RCTs gave intra-
venous injection of TXA.
11,22
Among all the five included
trials, four RCTs reported operative time of less than an
hour for arthroscopic ACLR surgery.
11,19–22
Of all the
included five RCTs with a total of 580 patients, 291
patients were assigned to the TXA group and 289 patients
were assigned to the control group.
11,19–22
The dosage of
TXA ranged from 1 to 3 gram across all the included RCTs.
Figure 1. PRISMA flow diagram.
Tan et al. 3
The clinical characteristics, dosage of TXA, route of
administration and baseline characteristics of the included
studies are outlined in Table 1. All the findings of primary
and secondary outcomes are reported in Table 2.
Risk of bias in included studies
The risk of bias assessment for all the included studies are
summarised in Figure 2. All the five studies demonstrated
low risk of bias in the domains of random sequence gener-
ation and incomplete outcome data. High risk of allocation
concealment was detected in Felli 2019 as they acknowl-
edged the risk of accidental bias during the treatment allo-
cation process.
19
Primary outcome
Four RCTs with a total sample size of 532 patients exam-
ined the postoperative blood loss in the arthroscopic ACRL
surgery.
11,19–22
Our analysis demonstrated that the use of
intra-articular or intravenous TXA reduced approximately
80 ml of postoperative blood loss in comparison to the
placebo group (MD: 81.93 ml [95%CI 141.80 to
22.05], p¼0.007). However, statistical heterogeneity
was observed as substantial (I
2
¼95%).
Secondary outcomes
In comparison to the placebo, the TXA group was associ-
ated with a significant lower postoperative VAS score
(studies ¼5, patients ¼580, MD: 1.39 [95%CI, 2.54
to 0.25], p¼0.02).
19–22
Heterogeneity was assessed as
substantial (I
2
¼96%).
All the included RCTs reported on the number of
patients requiring postoperative knee aspiration.
11,19–22
Our pooled data revealed that patients randomised to
TXA was associated with lower incidence of needing
knee aspiration than the placebo group (studies ¼5,
patients ¼580, OR: 0.19 [95%CI, 0.08 to 0.46], p¼
0.0002; I
2
¼0%).
In term of range of knee movement, patients who
received TXA were associated with greater degree of knee
movement than the placebo group (studies ¼5, patients ¼
580, MD: 2.86 [95%CI, 0.54 to 5.18]; p¼0.02; I
2
¼
0%).
11,19–22
The TXA group was also significantly associ-
ated with higher Lysholm score as compared to the placebo
group (studies ¼3, participants ¼233, MD: 7.38 [95%CI
2.75 to 12.01], p¼0.002; I
2
¼69%).
11,19,21
Two RCTs (a total number of 405 patients) investigated
the use of TXA in the severity of haemarthrosis.
11,20
In
comparison to the placebo group, our analysis showed that
the TXA group was significantly associated with higher
incidence of the lowest severity of haemarthrosis grade 0
(OR: 4.58 [95%CI, 3.86 to 35.12, p< 0.0001]) and 1 (OR:
11.64 [95%CI,2.82to7.45,p< 0.00001); and lower
incidence of severe haemarthrosis grade 2 (OR: 0.61
Table 1. Baseline characteristics of all the included studies.
First Author Year Country Study Type
Route of
administration Dose of TXA
Total
sample
size
Mean Age (Year +SD)
Mean operative Time,
min (+SD) Mean BMI (+SD)
TXA Control TXA Control TXA Control
Karaaslan
11
2015 Turkey Single Centre
RCT
Intravenous 15 mg/kg, followed
by 10 mg/kg for
3 hours
105 28.23 +6.6 28.3 +9.0 40.0 +18.0 15.0 +15.0 NR NR
Felli
19
2019 United State Single Centre
RCT
Intravenous 15 mg/kg 80 30.7 +11.0 32.0 +10.5 45.0 +6.6 40.8 +12.8 22.3 +3.0 22.7 +2.9
Chiang
20
2019 Taiwan Single Centre
RCT
Intra-articular 1 gram 304 25.7 +8.4 27.6 +6.9 54.5 +17.2 50.3 +19.3 NR NR
Pande
21
2019 India Single Centre
RCT
Intravenous 1 gram 48 NR NR 43.0 +8.0 45.0 +10.0 NR NR
Lee
22
2020 Republic of Korea Single Centre
RCT
Intra-articular 3 gram 60 30.3 +9.0 25.1 +8.1 NR NR 26.5 +2.8 25.5 +3.3
TXA: tranexamic acid group; SD: standard deviation; BMI: body mass index; NR: not reported; RCT: randomised controlled trial.
4Journal of Orthopaedic Surgery 29(2)
[95%CI,0.39to0.96,p¼0.03), grade 3 (OR: 0.41
[95%CI, 0.25 to 0.67, p¼0.003) and grade 4 (OR: 0.13
[95%CI, 0.06 to 0.29, p< 0.00001).
Subgroup analysis
In the subgroup analysis based on the route of TXA admin-
istration, the outcomes of VAS pain score (studies ¼2,
patients ¼347, MD: 2.23 [95%CI, 4.78 to 0.32, p¼
0.09) and range of knee movement (studies ¼2, patients ¼
347, MD: 0.92 [95%CI, 5.24 to 7.09, p¼0.77) became
non-significant in the intra-articular TXA group as com-
pared to the intravenous TXA group. The results of these
interactions may be skewed due to limited studies of small
sample size. For our primary outcome (postoperative blood
loss), both the findings of intra-articular (studies ¼2,
Table 2. Summary of findings for primary and secondary outcomes.
No Outcomes Trials N
I
2
(%)
Effect
Model MD/OR (95% CI) p-value
1
1.1
Estimated Blood Loss (mL)
11,19,20,22
Subgroup analysis by type of surgeries
Intra-articular injection
Intravenous administration
Heterogeneity: Tau
2
¼3053.37; ChI
2
¼58.37, df ¼3
(p< 0.0001), I
2
¼95%
Test for overall effect Z ¼2.68 (p¼0.007)
Test for subgroup differences: ChI
2
¼5.17, df ¼1(p¼0.02),
I
2
¼80.7%
4
2
2
532
347
185
95
0
95
REM
REM
REM
81.93 (141.80, 22.05)
25.04 (42.10, 7.99)
109.56 (180.40, 38.72)
0.007
0.004
0.002
2
2.1
Postoperative VAS Pain Score
11,19,22
Subgroup analysis by type of surgeries
Intra-articular injection
Intravenous administration
Heterogeneity: Tau
2
¼1.59; ChI
2
¼101.21, df ¼4
(p, 0.00001); I
2
¼96%
Test for overall effect: Z ¼2.38 (p¼0.02)
Test for subgroup differences: ChI
2
¼0.89, df ¼1(p¼0.34),
I
2
¼0%
5
2
3
580
347
233
96
96
77
REM
REM
REM
1.39 (2.54, 0.25)
2.23 (4.78, 0.32)
0.97 (1.59, 0.34)
0.02
0.09
0.01
3
3.1
Postoperative Range of Motion ()
11,29,22
Subgroup analysis by type of surgeries
Intra-articular injection
Intravenous administration
Heterogeneity: ChI
2
¼1.18, df ¼4(p¼0.88); I
2
¼0%
Test for overall effect: Z ¼2.42 (p¼0.02)
Test for subgroup differences: ChI
2
¼0.44, df ¼1(p¼0.51),
I
2
¼0%
5
2
3
580
347
233
0
0
0
FEM
FEM
FEM
2.89 (0.54, 5.18)
0.92 (5.24, 7.09)
3.18 (0.68, 5.68)
0.02
0.77
0.01
4
4.1
Incidence of Joint Aspiration
11,19,22
Subgroup analysis by type of surgeries
Intra-articular injection
Intravenous administration
Heterogeneity: ChI
2
¼0.92, df ¼2(p¼0.63); I
2
¼0%
Test for overall effect: Z ¼3.79 (p¼0.0001)
Test for subgroup differences: Not applicable
5
2
3
580
347
233
0
NA
0
FEM
FEM
FEM
0.19 (0.08, 0.44)
NE
0.19 (0.08, 0.44)
0.0001
NE
0.0001
5 Haemarthrosis Grade 0
11,20
2 405 23 FEM 11.64 (3.86, 35.12) <0.0001
6 Haemarthrosis Grade 1
11,20
2 405 0 FEM 4.58 (2.82, 7.45) <0.00001
7 Haemarthrosis Grade 2
11,20
2 405 0 FEM 0.61 (0.39, 0.96) 0.03
8 Haemarthrosis Grade 3
11,20
2 405 25 FEM 0.41 (0.25, 0.67) 0.0003
9 Haemarthrosis Grade 4
11,20
2 405 55 FEM 0.13 (0.06, 0.29) <0.00001
11 Postoperative Lysholm Score
11,19,21
3 233 69 REM 7.38 (2.75, 12.01) 0.002
MD: mean difference; OR: odds ratio; REM: random-effect model; FEM: fixed-effect model; NA: not applicable; NE: not estimated.
Tan et al. 5
patients ¼347, MD: 25.04 [95%CI, 42.10 to 7.99,
p¼0.004) and intravenous TXA (studies ¼2, patients ¼
347, MD: 109.56 [95%CI, 180.40 to 38.72,
p< 0.0001) groups remained significant.
Discussion
Our meta-analysis demonstrated that the use of TXA
reduced postoperative blood loss and incidence of needing
knee aspiration with lower pain score. Patients who rando-
mised to TXA were also noted to have significant lower
incidence of severe haemarthrosis than the placebo group.
However, the present systematic review needs to be inter-
preted with caveats due to small sample size, high risk of
bias in some of the included studies, substantial degree of
heterogeneity and non-standardised dosage of TXA. Due to
the limited available RCTs in the literature, the present
review included both intravenous and intra-articular route
of administration of TXA. It is believed that the intra-
articular administration of TXA will be associated with
lower plasma TXA level than intravenous injection of
TXA, resulting in lower systemic adverse events (incidence
of thromboembolism or stroke) of TXA.
27–30
A recently
published meta-analysis of 71 RCTs (7539 patients) also
concluded that topical use of TXA reduced intraoperative
blood loss and blood transfusion in surgical patients with-
out any notable adverse events associated with TXA.
18
The present meta-analysis reported that TXA reduced
postoperative blood loss (approximately 80 ml) in patients
undergoing arthroscopic ACLR surgery. This seems like a
negligible amount of blood loss to an adult, however the
accumulation of such amount of blood loss in the operated
knee joint will result in severe joint complications, such as
haemarthrosis and septic arthritis.
31
The finding in this
study was similar to other meta-analyses examining the use
of intravenous TXA in the reduction of postoperative blood
loss, incidence of blood transfusion without any notable
thromboembolic risk.
14,32–35
However, it remains unclear
regarding the optimal safe dose of TXA for intra-articular
joint injection. Parker and colleagues reported that intra-
articular TXA injection >20 mg/ml or more than 3 g into
joint could be cytotoxic to the chondrocytes, which may
impair recovery process of joint postoperatively.
36,37
Sub-
stantial heterogeneity was also observed in this measured
outcome due to limited trials of small sample size and
inclusion of different route of TXA administration. Differ-
ent route of TXA administration in orthopaedic surgeries is
still debatable. A meta-analysis by Montroy and co-
workers demonstrated no significant difference in term of
postoperative blood loss and incidence of blood transfusion
between both the intravenous TXA and topical TXA
groups.
38
The subgroup analysis in the present review
demonstrated similar positive effects of intra-articular and
intravenous injection of TXA in the reduction of postopera-
tive blood loss. However, no data of adverse events asso-
ciated with intra-articular or intravenous TXA was
available for data analysis. In contrast, the most updated
systematic review and meta-analysis by Li and colleagues
comparing intravenous versus intra-articular TXA in total
knee replacement surgery reported greater reduction of
intraoperative blood loss and incidence of blood transfu-
sion in those who received intra-articular TXA.
39
Thus,
future adequately powered RCTs are warranted to fill
knowledge gap with regard to the efficacy and safety of
different route of TXA administration in arthroscopic
ACLR surgery. Of note, the threshold of blood transfusion
varies from one study to another, which may potentially
introduce variances to the finding.
The present systematic review found that TXA patients
were associated with lower incidence of needing knee
aspiration and lower severity of haemarthrosis than the
placebo group. Haemarthrosis is defined as bleeding into
the joint cavity due to intra-articular injury.
31
It is one of
the most common postoperative complication seen in an
arthroscopic orthopaedics surgery.
40
It can cause severe
postoperative pain, joint infection or damage to articular
cartilage, which impair the process of healing. A recent
review based on level 1 and level 2 evidences by Belk and
Figure 2. The Cochrane Risk of Bias summary of all the included
randomised clinical trials.
6Journal of Orthopaedic Surgery 29(2)
colleagues demonstrated that the introduction of TXA is
beneficial in improving severity of haemarthrosis in arthro-
scopic assisted orthopaedics surgery, and their results were
consistent with our findings.
41
In low grade haemarthrosis,
joint aspiration is required to withdraw effusion and pre-
vent tissue adhesion in the knee joint.
42
However, knee
arthrocentesis or knee washout is required for severe
haemarthrosis.
43
Pain secondary to the complication of
haemarthrosis can lead to muscle wasting as a result of
an ineffective strengthening exercise after surgery.
The present review showed that patients who rando-
mised to TXA were associated with lower postoperative
VAS pain score than those receiving placebo. The finding
was consistent with a trial conducted by Guerreiro and
co-workers where the TXA group was reported to have
lower postoperative pain score.
44
However, our finding
needs to be interpreted with caution due to substantial
degree of heterogeneity and limited RCTs of small sample
size. The subgroup analysis also revealed that the data
inclusion of intra-articular group with non-significant
postoperative VAS score may introduce variances to the
findings. VAS pain score is a numerical subjective mea-
surement of pain intensity.
45
It can be varied across differ-
ent individuals given the sametypeofpainstimulus,
depending on their pain threshold and perception of pain.
46
Several studies showed that VAS score is effective in the
assessment of acute pain score in patients undergoing knee
surgery.
44,47
Two RCTs demonstrated lower level of
inflammatory markers (IL ¼6 and C-reactive protein) in
the TXA group when compared to the placebo group in hip
replacement surgery.
48,49
We postulate that good post-
operative pain control can lead to greater degree of knee
movement and hasten recovery process.
50
In the present
meta-analysis, it is demonstrated that TXA group was also
reported to have greater range of knee movement and better
Lysholm score (knee function assessment) after surgery.
However, Belk and colleagues reported no significant dif-
ference in the range of knee movement between the TXA
and control groups with substantial heterogeneity.
There were some limitations to our review. The protocol
of TXA administration (dosage and route of TXA) varied
across all the included RCTs. All the included RCTs of
small sample size were not powered for our primary out-
come (postoperative blood loss). Different RCTs adopt dif-
ferent methods in estimating postoperative blood loss.
Three studies measured the amount of blood loss from the
drainage bottle. In contrast, Lee and colleagues used
haemoglobin-balance method to predict amount of blood
loss as no intra-articular drain was inserted in their patients.
In term of postoperative pain, there was no standardised
analgesia protocol among all the included RCTs, which can
contribute to high degree of heterogeneity. Two review
articles suggested that the route of intra-articular TXA
injection can be an alternative to intravenous TXA due to
lower risk of systemic adverse effects of TXA. Future ade-
quately powered trials are warranted to examine the
efficacy and safety of intravenous versus intra-articular
injection of TXA in the arthroscopic ACLR surgery.
Conclusion
In this meta-analysis, TXA reduced postoperative blood
loss with lesser incidence of needing knee aspiration along
with better range of knee movement and Lysholm score in
patients undergoing arthroscopic ACLR surgery.
Author contributions
TKT: Protocol/ project management, Data collection or manage-
ment, Data analysis, Manuscript writing/editing. KTN: Manu-
script writing/editing. HJN: Data collection or management.
SBH: Manuscript writing/editing. RR: Manuscript writing/
editing.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Tze Khiang Tan https://orcid.org/0000-0001-5446-5135
Hui Jane Lim https://orcid.org/0000-0003-3579-4587
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