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Low- and high-dose TXA effective in reducing blood loss and transfusion needs in TKA
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March 2014
Low- and high-dose TXA effective in reducing blood loss and transfusion needs in TKA
Study Type:Randomized Trial
OE Level Evidence:1
Journal Level of Evidence:N/A
Efficacy of low-dose intra-articular tranexamic acid in total knee replacement; a prospective triple-blinded randomized controlled trial
BMC Musculoskelet Disord. 2013 Dec 5;14:340. doi: 10.1186/1471-2474-14-340Did you know you're eligible to earn 0.5 CME credits for reading this report? Click Here
Synopsis
135 patients scheduled for total knee arthroplasty were randomized to three different hemostasis protocols with 2 hour postoperative drain clamping: 1) a 250mg intra-articular tranexamic acid (IA-TXA) injection (low-dose), 2) a 500mg IA-TXA injection (high-dose), or 3) a placebo injection. The purpose was to determine the effect of different TXA doses on reducing blood loss and transfusion needs. The results indicated that both TXA doses significantly reduced calculated blood loss and transfusion requirements compared to the placebo group. Furthermore, blood loss was similar between TXA groups, although fewer transfusions were needed in those who received 500mg TXA. The latter of the two findings may have been impacted by significantly lower preoperative hemoglobin levels in the 250mg TXA group.
Publication Funding Details
+
Funding:
Not Reported
Conflicts:
None disclosed
Was the allocation sequence adequately generated?
Was allocation adequately concealed?
Blinding Treatment Providers: Was knowledge of the allocated interventions adequately prevented?
Blinding Outcome Assessors: Was knowledge of the allocated interventions adequately prevented?
Blinding Patients: Was knowledge of the allocated interventions adequately prevented?
Was loss to follow-up (missing outcome data) infrequent?
Are reports of the study free of suggestion of selective outcome reporting?
Were outcomes objective, patient-important and assessed in a manner to limit bias (ie. duplicate assessors, Independent assessors)?
Was the sample size sufficiently large to assure a balance of prognosis and sufficiently large number of outcome events?
Was investigator expertise/experience with both treatment and control techniques likely the same (ie.were criteria for surgeon participation/expertise provided)?
Yes = 1
Uncertain = 0.5
Not Relevant = 0
No = 0
The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.
3/4
Randomization
4/4
Outcome Measurements
4/4
Inclusion / Exclusion
4/4
Therapy Description
4/4
Statistics
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65
The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.
Why was this study needed now?
Total knee arthroplasty is associated with considerable perioperative blood loss, oftentimes requiring allogenic transfusion. To reduce the requirement for transfusion with such procedures, tranexamic acid (TXA) has been used extensively. Due the risk of potential venous thromboembolic complications with intravenous TXA, intra-articular injections (IA-TXA) are becoming more popular. However, guidelines on IA-TXA use have yet to be established, particularly with regards to dosage.
What was the principal research question?
Does low dose IA-TXA (250mg) reduce perioperative blood loss and transfusion requirements compared to placebo and, if so, how does its efficacy compare to high dose IA-TXA (500mg)?
Study Characteristics
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Population:
135 patients with primary knee osteoarthritis and undergoing conventional total knee arthroplasty. The NexGen Gender prosthesis (Zimmer Inc., Warsaw, Indiana, USA) was used for female patients, and the NexGen Flex prosthesis (Zimmer Inc.) was used for male patients. Tourniquet use was applied at the proximal thigh at a pressure of 350mmHg. All procedures were performed with a midline incision, medial parapatellar arthrotomy, and midvastus incision, and were cemented with Palacos bone cement (Hevaeus Medical GmbH, Germany). A high pressure vacuum drain system (Drainobag 600V Lock, B-Braun, Milsungen AG, Germany) was placed deep into the knee joint, followed by fascia closure.
Intervention:
TXA 250mg: Following fascia closure, patients received a 250mg dose of TXA (5mL of 250mg per 5mL, Transmin, OLIC Ltd, Ayutthaya, Thailand) injected into the knee joint through the drain tube. TXA solution was prepared in physiologic saline to a total volume of 25mL. The vacuum drain was connected to the drain tube and clamped for 2 hours (Mean age: 67.6 +/- 8.7) (n=45; 42 female)
Comparison:
TXA 500mg: Following fascia closure, patients received a 500mg dose of TXA (10mL of 250mg TXA per 5mL, OLIC Ltd.) injected into the knee joint through the drain tube. TXA solution was prepared in physiologic saline to a total volume of 25mL. The vacuum drain was connected to the drain tube and clamped for 2 hours (Mean age: 68.1 +/- 6.2) (n=45; 40 female)
Control: Following fascia closure, patients received a placebo injection containing 25mL of physiologic saline only. The vacuum drain was connected to the drain tube and clamped for 2 hours (Mean age: 66.2 +/- 7.3) (n=45; 43 female)
Outcomes:
Postoperative data of drainage volume, hematocrit values (Hct), hemoglobin levels (Hb), incidence of blood transfusion, and blood loss were recorded. Blood transfusions were considered when Hb was less than 8 gm% or patient had positive symptoms of anemia (dyspnea, tachypnea, and hypoxemia). Postoperative blood loss was measured via three different methods: drainage blood loss (DBL), total Hb loss (THL),, and calculated total blood loss (CTBL). Drainage blood loss rate (DBLR), and accumulated drainage volume (ADV) were also measured. Duplex ultrasound was used to document cases of deep vein thrombosis and computer tomographic angiogram was performed to confirm diagnosis of pulmonary embolism; both were recorded as venous thromboembolic (VTE) complications. The Knee Society Knee Score (KSKS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess functional outcome. Postoperative complications were also documented.
Methods:
RCT, Triple-blind, Single-center, Prospective
Time:
Hematologic outcomes were assessed for 48 hours following clamp release. Functional outcome was assess at 3, 6, and 12 months postoperatively.
What were the important findings?
- Mean total Hb loss among both the TXA 250mg (2.2g/dL) and TXA 500mg (2.2g/dL) groups was significantly lower compared to the control group (2.7g/dL) (both p<0.001). However, the difference in mean drainage blood loss did not reach significance between the TXA 250mg group (475.0mL) and control group (546.9mL), nor between the TXA 500mg group (430.2mL) and control group (p=0.09).
- The mean calculated total blood loss was measured at 239.7mL for the TXA 250mg group and 217.2mL for the TXA 500mg group, both of which were significantly lower than that calculated in the control group (329.2mL).
- The requirement for allogeneic blood transfusion was significantly lower in the TXA 500mg group, with 0 patients needing transfusion compared to 6 patients of the TXA 250mg group (13%) and 10 patients of the control group (27%) (p=0.005).
- Accumulated drainage volume (ADV) was significantly lower in the TXA 250mg group compared to the control group for 12 hours following clamp release, and in the TXA 500mg compared to the control group for 20 hours following clamp release (both p<0.05).
- Mean drainage blood loss rate (DBLR) was significantly lower in the TXA 250mg group compared to the control group for the first 2 hours after clamp release and in the TXA 500mg group compared to the control groups for 4 hours following clamp release (both p<0.05). After the first 4 hour time interval following clamp release, the mean DBLR was significantly greater in both TXA groups compared to the control group from 8-20 hours (p<0.05).
- Four cases of VTE were documented in the control group (1 PE; 3 DVT), one case in the TXA 250mg group (1 DVT), and two cases in the TXA 500mg group (2 DVT). The incidences of VTE were not significantly different from group to group.
- There were no significant differences between groups in functional outcome (on both KSKS and WOMAC) over the 1-year follow-up of these measurements.
- The TXA-500 group showed significantly higher preoperative Hb levels compared with TXA-250 group (p=0.02).
What should I remember most?
Both intra-articular low dose (250mg) and high dose (500mg) tranexamic acid with a 2-hour clamping protocol significantly reduced total blood loss and the requirement for allogenic blood transfusion following total knee arthroplasty compared to placebo injection.
How will this affect the care of my patients?
In total knee arthroplasty, intra-articular tranexamic acid, 250mg of 500mg, followed by 2 hour postoperative drain clamping appears to be an effective hemostasis protocol. Total blood loss was calculated to be significantly reduced, without an increase in postoperative complications. Transfusions were needed less often in the 500mg TXA group compared to the 250mg group, although preoperative hemoglobin levels may have impacted this finding. Further research should be conducted to definitely characterize the efficacy and safety profiles of low- and high-dose tranexamic acid protocols.
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Orthopaedic Surgeon - Canada
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