What literature is there to support oral tranexamic acid versus IV for orthopedic procedures (hip, knee, shoulder) as well as scoliosis surgeries?

Comment by InpharmD Researcher

A meta-analysis suggests that multiple-dose oral TXA (e.g., 2 g preoperatively followed by 1 g doses postoperatively) is a safe and effective strategy for managing perioperative blood loss in total joint replacement patients. However, there was a wide range of doses studied, and the optimal dosing regimen is not yet fully established. In particular, the timing of TXA is seldom discussed.

Background

As a synthetic derivative of amino acid lysine, tranexamic acid (TXA) competitively inhibits the plasminogen activator, leading to ​​the antifibrinolytic effect. At low oral doses, 50% of TXA is absorbed through the gastrointestinal tract. TXA decreases intraoperative blood loss in multiple studies and diminishes blood loss after surgical removal of third molars in healthy patients. Concerns over thromboembolism after systemic intravenous (IV) administration makes the oral formulation an attractive option due to less systemic absorption leading to a lower incidence of thromboembolic complications. Overall, the oral formulation is well-tolerated and easy to administer. However, given the variability in oral dosing regimens across clinical studies, more evidence is required to establish an optimized dosing strategy. [1], [2]

A 2018 randomized controlled trial (N= 100) assessed the blood loss and cost-effectiveness of the oral and IV administration of TXA for the treatment of primary total hip arthroplasty (THA). Eligible patients who underwent primary THA were randomized 1:1 to receive either 1 g of IV TXA (n= 50; 10 minutes before the incision, and three and six hours postoperatively) or 1 g (2 tablets of 500 mg) of oral TXA (n= 50; two hours before the incision, and three and six hours postoperatively) with a total follow-up over six months. All patients also received regular deep vein thrombosis (DVT) prophylaxis with low molecular-weight heparin (0.2 mL, 2,000 IU) subcutaneously six hours postoperatively, followed by a full dose of 0.4 mL (4,000 IU) every 24 hours until discharge. Upon discharge, oral rivaroxaban 10 mg daily was continued for 15 days if no bleeding was identified. The study did not identify any significant changes between the oral TXA vs IV TXA groups in total blood loss (863.3 ± 272.5 mL vs 886.1 ± 200.2 mL, p= 0.66), maximum hemoglobin drop (2.9 ± 0.6 g/dL and 3.1 ± 0.8 g/dL, p= 0.17), maximum hematocrit drip, and transfusion rates and units. Even though the costs associated with oral TXA were significantly lower in the oral TXA group vs IV TXA group (¥600 and ¥3,150, p<0.01), as the monetary evaluation was based on Chinese ¥, this specific cost-effectiveness analysis may not be readily applicable to the US practice settings. During the follow-up, no significant differences in hospital length of stay, DVT and/or pulmonary embolism (PE), and wound complications were noted between the two interventions. The authors concluded that oral TXA may be a better alternative to the IV form in primary THA; however, since blood values were not explicitly collected and evaluated after the postoperative anticoagulant therapy, the effects of early anticoagulation with TXA remain uncertain based on the study results. [3]

A 2019 meta-analysis of 10 randomized controlled trials (N= 1,140 patients) evaluated the efficacy and safety of oral versus IV TXA in reducing blood loss in primary total knee and hip arthroplasty. Eligible participants, all diagnosed with joint degenerative diseases, were allocated to either oral TXA (557 patients) or IV TXA (583 patients) groups. The total oral doses used for TXA included 1950 mg, 2 g, or 3 g. The frequency of administration ranged from 1-4 doses. There appears to be a lack of consensus regarding the optimal timing and dosing of oral TXA. Based on the author’s analysis, they suggest that 2 g oral TXA was effective for reducing blood loss during total joint replacement, regardless of the dosing frequency. The role of higher doses requires validation in high-quality studies. [4]

In response to the lack of consensus, a 2020 meta-analysis was conducted regarding the optimal dosing regimen for oral TXA. A total of 9 randomized controlled trials (N= 1,678 patients) were included for analysis. Among the TXA groups, dosing regimens varied from one to five administrations, with 2 g of TXA administered preoperatively followed by 1 g doses at different intervals postoperatively in most studies. Oral TXA demonstrated significant reductions in blood loss, hemoglobin decline, transfusion rates, length of hospital stay, and incidence of thromboembolic events. Notably, five administrations of TXA appeared more effective than four; however, data supporting this finding were limited. The analysis highlighted variability in dosing strategies across studies, with most employing 2 g as the initial dose, followed by subsequent administrations within the first 24 hours postoperatively. Despite limitations such as geographical concentration (all studies conducted in China) and the lack of longer-term follow-up, the meta-analysis supports the use of multiple-dose oral TXA as a safe and effective strategy for managing perioperative blood loss in total joint replacement patients. [5]

References:

[1] Eftekharian HR, Rajabzadeh Z. The Efficacy of Preoperative Oral Tranexamic Acid on Intraoperative Bleeding During Rhinoplasty. J Craniofac Surg. 2016;27(1):97-100. doi:10.1097/SCS.0000000000002273
[2] Wang D, Wang HY, Luo ZY, Pei FX, Zhou ZK, Zeng WN. Finding the Optimal Regimen for Oral Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial. J Bone Joint Surg Am. 2019;101(5):438-445. doi:10.2106/JBJS.18.00128
[3] Wu Y, Zeng Y, Hu Q, et al. Blood loss and cost-effectiveness of oral vs intravenous tranexamic acid in primary total hip arthroplasty: A randomized clinical trial. Thromb Res. 2018;171:143-148. doi:10.1016/j.thromres.2018.10.006
[4] Ye W, Liu Y, Liu WF, Li XL, Fei Y, Gao X. Comparison of efficacy and safety between oral and intravenous administration of tranexamic acid for primary total knee/hip replacement: a meta-analysis of randomized controlled trial. J Orthop Surg Res. 2020;15(1):21. Published 2020 Jan 20. doi:10.1186/s13018-019-1528-8
[5] Ye W, Liu Y, Liu WF, Li XL, Shao J. The optimal regimen of oral tranexamic acid administration for primary total knee/hip replacement: a meta-analysis and narrative review of a randomized controlled trial. J Orthop Surg Res. 2020;15(1):457. Published 2020 Oct 6. doi:10.1186/s13018-020-01983-1
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What literature is there to support oral tranexamic acid versus IV for orthopedic procedures (hip, knee, shoulder) as well as scoliosis surgeries?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-6 for your response.

 

Intravenous and oral tranexamic acid are equivalent at reducing blood loss in thoracolumbar spinal fusion: a prospective randomized trial

Design

Single-center, prospective, randomized trial

N= 83

Objective

To compare perioperative blood loss in patients undergoing elective posterior thoracolumbar fusion who were treated with intravenous (IV) versus oral (PO) tranexamic acid (TXA)

Study Groups

IV-TXA (n= 43)

PO-TXA (n= 40)

Inclusion Criteria

Age ≥ 18 years old; undergoing elective posterior thoracolumbar instrumented spinal fusions

Exclusion Criteria

Having known allergy to TXA; history of renal failure or kidney transplant; history of arterial thromboembolic event within the past year; placement of an arterial stent within the past year; a history of thromboembolic event, coagulopathy, or refusal to receive blood products

Methods

Eligible patients undergoing thoracolumbar fusion were randomized to receive 1.95 g of oral TXA two hours preoperatively or 2 g IV TXA (1 g before incision and 1 g before wound closure) intraoperatively. The sample was further stratified into three categories based on number of levels fused (1-2 level fusions, 3-5, and > 5). Intraoperative blood transfusion was given if hemoglobin (Hgb) dropped below 7.0 g/dL or at the anesthesiologist’s discretion. No patient was lost or excluded during the follow-up period.

Duration

Enrollment: February 2017 to December 2017

Outcome Measures

Primary outcome: reduction of hemoglobin (Hgb)

Secondary outcomes: calculated blood loss, drain output, postoperative transfusion, complications, and length of hospital stay

Baseline Characteristics

  

IV-TXA (n= 43)

PO-TXA (n= 40)

 p-value

Age, years

 64 ± 13 61 ± 12 0.19

Female

24 (55.8%) 25 (62.5%) 0.54

Body mass index (BMI), kg/m2

 28.5 ± 5.7 32.1 ± 5.8 0.006

Number of fused levels

1-2 levels

3-5 levels

> 5 levels

3.8 ± 3.0

18

15

10

3.7 ± 2.9

20

12

8

0.89

--

--

-- 

Pre-operative levels

Hgb (g/dL)

Hct (%)

Platelet count

 

13.1 ± 1.7

38.6 ± 6.4

205 ± 61

 

13.2 ± 1.8

39.7 ± 5.8

240 ± 53

 

0.82

0.76

0.008

Intra-operative measures

Anesthesia time, min

Surgical time, min

Number receiving blood transfusion

 

363 ± 127

267 ± 122

4 (9%)

 

371 ± 121

277 ± 119

2 (5%)

 

0.76

0.69

0.45 

Results

Endpoint

IV-TXA (n= 43)

PO-TXA (n= 40)

p-value

Hgb drop, g/dl

 3.36 ± 1.82 3.43 ± 1.75 0.01

Calculated blood loss, ml

 1,235 ± 672 1,312 ± 748 0.02

Postop transfusion

 19% 13% 0.44 

Complications

DVT/PE

Infection

 

2%

7%

 

3%

5%

 

0.96

0.71

Length of hospital stay, days

4.5 ± 2.8

4.1 ± 3.4

 0.64

Adverse Events

 Refer to results section

Study Author Conclusions

In the setting of spine thoracolumbar fusions, oral tranexamic acid produced an equivalent reduction in hemoglobin and blood loss compared to its intravenous counterpart. Given the equivalent clinical outcomes, potential cost savings, and the ease of drug administration, oral tranexamic acid is a superior alternative to intravenous tranexamic acid.

InpharmD Researcher Critique

While heterogeneity was minimized by sub-stratification of the number of fusion levels into three categories, the study still had varying patient diagnosis and surgical technique (single surgeon performed most of the cases (93% vs 85% for IV vs PO). Additionally, the study was not controlled by a placebo group.



References:

Yu CC, Kadri O, Kadado A, et al. Intravenous and Oral Tranexamic Acid Are Equivalent at Reducing Blood Loss in Thoracolumbar Spinal Fusion: A Prospective Randomized Trial. Spine (Phila Pa 1976). 2019;44(11):755-761. doi:10.1097/BRS.0000000000002954

 

Oral tranexamic acid for bleeding during spinal surgery: A randomized double-blind placebo clinical trial

Design

Randomized, double-blind, single-centered, placebo-controlled clinical trial

N= 129

Objective

To evaluate the effect of oral Tranexamic acid (TXA) on the amount of bleeding during spinal surgery

Study Groups

TXA (n= 64)

Placebo (n= 65)

Inclusion Criteria

Age 20 to 75 years, lacking cardiovascular disease, having discopathies with spinal fusion, and discopathies more than two levels or having a two-sided spinal cord

Exclusion Criteria

Abnormal bleeding (e.g., history of petechiae hemoptysis, purpura, hematemesis), a platelet count < 150,000 (k), history of thrombosis or embolism, severe allergies, use of intermittent medications with hemostasis in the blood, uncontrolled high blood pressure (BP > 160/90), obesity (BMI > 30)

Methods

Patients were randomized to 25 mg/kg of oral TXA divided over four doses a day before the surgery and 500 mg on the morning of the surgery or equivalent placebo. Coagulation was checked during and for 72 hours after the operation, and coagulation products were administered if necessary. Patients were followed up until discharge.

Duration

Follow-up: various (until discharge)

Outcome Measures

Amount of bleeding during surgery, hemoglobin (Hb) levels, PTT levels, PT levels, hospitalization duration, the blood lost from drains, the incidence of nausea and vomiting after surgery

Baseline Characteristics

  

TXA (n= 64)

Placebo (n= 65)

  

Age, years

 44.68 ± 11.99  42.99 ± 11.79  

Female

60 (46.5%) (N= 129)  

Results

Endpoint

TXA (n= 64)

Placebo (n= 65)

p-value

Effect of oral TXA on different variables

Amount of bleeding, ml

Hb levels one day after surgery

PTT levels

PT levels

Hospitalization duration, numbers

Amount of blood lost from drains (50 cc for each drain line)

 

410.8 ± 271.3

11.2 ± 1.1

34.7 ± 4.6

1.3 ± 0.1

3.5 ± 1.1

177.7 ± 77.1 

 

824.3 ± 475.9

11.1 ± 1.1

31.7 ± 3.3

1.2 ± 0.2

4 ± 1.5

210.1 ± 84.1

 

0.0002

0.447

0.0001

0.252

0.0001

0.018 

Mean Hb level after spinal surgery

Before

After

 

12.8

11.2

 

12.3

11.1

 

0.002 (TXA before vs. after)

0.003 (placebo before vs. after)

Frequency of nausea and vomiting

 24/64 (37.5%) 4/65 (6.2%) 0.0001

Adverse Events

 See results section above

Study Author Conclusions

Oral TXA significantly reduced the amount of bleeding during and after surgery and the duration of hospitalization in patients undergoing spinal surgery. Due to its anti-fibrinolytic properties, TXA helps control bleeding effectively. Consequently, the amount of intraoperative bleeding decreases with the administration of the TXA, but related nausea and vomiting can affect the acceptance of routine use of TXA in patients. This medication has no effect on Hb changes and coagulation tests after the operation.

InpharmD Researcher Critique

This was a single-center study done in Iran with a relatively small sample size. Operations may have been performed by different surgeons and anesthetists, possibly introducing confounding variables. 



References:

Saleh Rasras, Nour Mohammad Mamizadeh, Hossein Safari, et al. Oral tranexamic acid for bleeding during spinal surgery: A randomized double-blind placebo clinical trial[J]. AIMS Medical Science, 2020, 7(2): 57-68. doi: 10.3934/medsci.2020005

 

Finding the Optimal Regimen for Oral Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial

Design

Randomized, double-blind, single-center, placebo-controlled trial

N= 200

Objective

To assess the efficacy of a regimen of multiple doses of oral tranexamic acid (TXA) on blood loss in primary total hip arthroplasty

Study Groups

Control (n= 50)

Group B (n= 50)

Group C (n= 50)

Group D (n= 50)

Inclusion Criteria

 Age ≥ 18 years; scheduled to undergo primary unilateral total hip arthroplasty

Exclusion Criteria

Diagnosis other than osteoarthritis or osteonecrosis of the femoral head; known allergy to TXA; use of spinal anesthesia; history of hematopoietic or hemorrhagic disorder; history of deep venous thrombosis (DVT) or pulmonary embolism (PE); treatment with anticoagulants within 1 week prior to surgery

Methods

Patients undergoing total hip arthroplasty were randomized to one of four groups. All patients received oral TXA 2 g two hours preoperatively. Groups differed in postoperative TXA schedules, with placebo tablets given when TXA was not.

  • Group A (control): placebo tablets 3, 9, and 15 h post-operation;
  • Group B: TXA 1 g at 3 h post-operation;
  • Group C: TXA 1 g at 3 and 9 h post-operation;
  • Group D: TXA 1 g at 3, 9, and 15 h post-operation.

All patients also received topical TXA 1 g during surgery. Surgery was performed by two senior surgeons using a posterolateral approach and a single brand of cementless acetabular and femoral components. No postoperative drain was used. 

A standard blood transfusion protocol was followed for all patients, where transfusion was used for a Hb level < 7 g/dL in asymptomatic patients or < 10 g/dL in patients who developed any anemia-related organ dysfunction, intolerable symptoms of anemia, or ongoing blood loss.

Following surgery, patients received thromboprophylaxis with enoxaparin (2000 IU after 8 hours, then 4000 IU daily) and rivaroxaban 10 mg for 10 days following discharge. Mechanical thromboprophylaxis was also used the day after surgery.

Duration

 Follow-up: up to 3 months post-surgery

Outcome Measures

Primary: postoperative blood loss

Secondary: Hb reduction; intraoperative blood loss; hospital stay; transfusion requirement

Baseline Characteristics

  

Control (n= 50)

Group B (n= 50)

Group C (n= 50)

Group D (n= 50)

 p-value

Age, years

 64.41 ± 13.94 66.98 ± 9.71 66.76 ± 9.87 63.94 ± 12.37 0.433

Female

74% 70% 66% 72% 0.840
Body mass index, kg/m2 25.11 ± 4.26 24.89 ± 3.39

24.44 ± 3.66

 25.51 ± 3.25 0.537

Preoperative laboratory values

Hb, g/dL

Hematocrit, L/L

 

13.44 ± 1.44

0.41 ± 0.04

 

13.32 ± 1.07

0.42 ± 0.03

 

13.66 ± 1.27

0.40 ± 0.03

 

13.48 ± 1.42

0.41 ± 0.04

 

0.645

0.193

There were no significant differences in any baseline characteristics or laboratory values, including hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, INR, D-dimer, or fibrinogen degradation product.

Results

 

Control (n= 50)

Group B (n= 50)

Group C (n= 50)

Group D (n= 50)

p-value

Total blood loss, mL

 983.55 ± 286.66 792.24 ± 292.99 630.84 ± 229.89 553.02 ± 186.07 <0.001

Reduction in Hb, g/dL

 3.28 ± 1.04 2.71 ± 0.89 2.17 ± 1.09 2.01 ± 0.99 <0.001

Intraoperative blood loss, mL

 175.75 ± 24.67 180.61 ± 32.52 174.01 ± 28.82 182.64 ± 29.37 0.405

Required transfusion

 1 (2%) 0 0 0 0.389

Length of hospital stay, days (Interquartile Range [IQR])

 4 (3-4) 3 (3-4) 4 (3-4) 4 (3-4) 0.154

The mean total blood loss was significantly less when postoperative TXA was given compared to the control group. Groups C and D (when TXA was given in multiple postoperative doses) also had a significantly lower blood loss than group B (p= 0.009 and p< 0.001, respectively).

There was no significant difference in total blood loss between groups C and D (mean difference 77.8 mL; 95% confidence interval -53.3 to 208.9 mL; p= 0.417).

Adverse Events

No patient experienced symptomatic DVT or PE within 90 days postoperatively.

Hematoma was reported in one patient (2%) each in groups A and B. Wound secretion was reported by one patient (2%) each in groups A and C. All adverse events were successfully resolved without sequelae or death.

Study Author Conclusions

Multiple postoperative doses of oral TXA further reduced blood loss compared with a single preoperative bolus. The regimen of a preoperative dose and three postoperative doses of oral TXA produced maximum effective reduction of blood loss in total hip arthroplasty.

InpharmD Researcher Critique

Strengths of this study include the sound randomization scheme, use of starch placebo tablets, and multigroup comparison. Additionally, two senior surgeons conducted the total hip arthroplasty on all patients, which reduces the chance of bias between surgeries. 

Limitations of this study include the relatively small sample size (n= 50 per group), single-center nature from an institution in China, and potential differences in postoperative management. All patients also received general anesthesia, so these results may not apply to patients who receive spinal anesthesia. Additionally, topical TXA was used preoperatively, which may have affected postoperative blood loss across all groups.



References:

Wang D, Wang HY, Luo ZY, Pei FX, Zhou ZK, Zeng WN. Finding the Optimal Regimen for Oral Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial. J Bone Joint Surg Am. 2019;101(5):438-445. doi:10.2106/JBJS.18.00128

 

Blood-conserving efficacy of multiple doses of oral tranexamic acid associated with an enhanced-recovery programme in primary total knee arthroplasty: a randomized controlled trial

Design

Single-center, four-arm, randomized, double-blind trial; (N= 200)

Objective

To identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA)

Study Groups

Group A: 2.0 g of TXA orally two hours preoperatively (n= 50)

Group B: a single dose of TXA followed by 1.0 g orally three hours postoperatively (n= 50)

Group C: a single dose of TXA followed by 1.0 g three and nine hours postoperatively (n= 50)

Group D: a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (n= 50)

Inclusion Criteria

Patients aged > 18 years who were scheduled for elective, unilateral, primary TKA

Exclusion Criteria

Diagnosis other than primary osteoarthritis (OA), absence of written informed consent, the use of spinal anesthesia, simultaneous bilateral TKAs, a history of medical comorbidity including deep vein thrombosis (DVT) or pulmonary embolism (PE), hematological disorders, current anticoagulant therapy (warfarin or heparin) within one week, and a history of allergy to TXA

Methods

Those in group A were given an oral dose of 2 g of TXA (four tablets of 500 mg) approximately two hours preoperatively and
then an oral form of 1 g of placebo pills (two tablets of 500 mg) identical in appearance, with no active ingredient, three, nine, and 15 hours postoperatively. Those in group B were given 2 g of oral TXA two hours preoperatively, 1 g of oral TXA three hours postoperatively, and 1 g of placebo nine and fifteen hours postoperatively. Those in group C were given 2 g of oral TXA two hours preoperatively, 1 g of oral TXA three and nine hours postoperatively, and 1 g of placebo 15 hours postoperatively. Those in group D were given 2 g oral TXA two hours preoperatively and 1 g of oral TXA three, nine, and 15 hours postoperatively.

All patients were managed using the same perioperative protocols.

Duration

June and October 2017

Outcome Measures

The primary outcome measure was total blood loss.

Secondary outcome measures were hidden blood loss (HBL), reduction in hemoglobin level, and adverse events. 

Baseline Characteristics

  

A (n= 50)

B (n= 50)

C (n= 50)

 D (n= 50)  

Mean age, yrs (SD)

 63.02 ± 14.14 65.60 ± 8.55 64.10 ± 11.36  63.42 ± 11.72  

Gender, male: female, n

 15/35 13/37 17/33 16/34  

ASA Classification

I

II

III

- 

11 (22%)

32 (64%)

7 (14%)

- 

12 (24%)

30 (60%)

8 (16%) 

-

10 (20%)

35 (70%)

5 (10%)

-

12 (24%)

31 (62%)

7 (14%)

  

Mean Hb, g/dL

 13.53 ± 1.41 13.31 ± 1.17 13.31 ± 1.28 13.44 ± 1.24  

No significant p-values in baseline characteristics.

ASA, American Society of Anesthesiologists. 

Results

Endpoint

A (n= 50)

B (n= 50)

C (n= 50)

D (n= 50)

p-value

Total blood loss, mL

 1,016.97 ± 331.89  832.28 ± 314.49 661.02 ± 262.38 597.69 ± 219.56 < 0.001

Hidden blood loss, mL

 890.11 ± 325.92 699.18 ± 319.52 533.12 ± 263.29 469.48 ± 221.84 < 0.001

Intraoperative blood loss, mL

 126.86 ± 26.64 133.10 (31.44) 127.91 ± 28.27 128.22 ± 24.12 0.681

Reduction of Hb, g/dL

 3.31 ± 1.12  2.75 (1.02) 2.22 ± 0.91 2.04 ± 0.95 < 0.001

Groups C (661.1 mL ± 262.4) and D (597.7 mL ± 219.6) had significantly lower mean total blood loss compared with groups A and B.

The mean HBL was significantly lower in groups B (699.2 mL), C (533.1 mL) and D (469.9 mL) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively).

Groups C (2.22 mL ± 0.91) and D (2.04 mL ± 0.95) had a lower reduction in the level of hemoglobin than groups A and B.

However, there were no differences between groups C and D in relation to the three parameters.

Adverse Events

Common Adverse Events: Wound secretion was reported in all (A,B,C,D) groups: 2%, 4%, 2%, 2%, respectively

Serious Adverse Events: Hematoma (n= 1; 2%) was reported in group B

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

In conclusion, a postoperative one-dose regimen of oral TXA is not the most effective regimen for reducing blood loss after primary TKA. Regimens involving an additional two or three doses produced a significant reduction in total blood loss and a lower decrease in the level of Hb, with no significant differences between the two regimens. Combining two postoperative doses with one preoperative dose of oral TXA is the least amount necessary for clinical efficacy. However, a regimen involving three postoperative doses produced the maximum reduction of blood loss. 

InpharmD Researcher Critique

This study was performed in China. Population and procedural differences may limit applicability to other settings. The estimation of the sample size was based on total blood loss, and there were no thromboembolic complications. The analysis was therefore likely underpowered.

 

References:

Wang D, Wang HY, Luo ZY, et al. Blood-conserving efficacy of multiple doses of oral tranexamic acid associated with an enhanced-recovery programme in primary total knee arthroplasty: a randomized controlled trial. Bone Joint J. 2018;100-B(8):1025-1032. doi:10.1302/0301-620X.100B8.BJJ-2017-1598.R1

 

The Efficacy of Preoperative Oral Tranexamic Acid on Intraoperative Bleeding During Rhinoplasty

Design

Double-blind, randomized, placebo-controlled clinical trial

N= 50

Objective

To evaluate the efficacy of oral tranexamic acid (TXA) on blood loss during rhinoplasty.

Study Groups

TXA (n= 25)

Placebo (n= 25)

Inclusion Criteria

Adults; American Society of Anesthesiologists (ASA) physical status I; undergoing rhinoplastic surgery

Exclusion Criteria

Systemic disease; history of any drug consumption; allergy to TXA; hemorrhagic disease; liver or renal dysfunction; concurrent use of  anticoagulant drugs; heart block or myocardial damage; morbid obesity (BMI ≥35)

Methods

Eligible patients were randomized 1:1 to receive either a 1 g (2x500 mg) tranexamic acid tablet or placebo two hours before starting the surgery. All patients were evaluated in the postanesthesia recovery room for the first six hours and in the ward for 12 hours for postoperative monitoring.

Duration

Not specified. 

Outcome Measures

Duration of operation, the amount of blood loss, surgeon’s satisfaction rate

Baseline Characteristics

  

TXA (n= 25)

Placebo (n= 25)

 p-value

Age, years

 24.72 ± 3.6 22.32 ±5.12 0.061

Female

17 (68%) 12 (49%) 0.152

BMI, kg/m2

 21.45 ±3.10 21.48 ± 2.41 0.964

Results

Endpoint

TXA (n= 25)

Placebo (n= 25)

p-value

Total blood loss, mL

 144.6 ± 60.28 199.6 ± 73.05 0.005

Duration of surgery, h

 2.60 ± 0.53 2.99 ± 0.59 0.017 

Surgeon’s satisfaction about surgery field*

 3.76 ± 0.52 2.16 ± 0.50 0.001 

* Surgeons satisfaction: (1: poor, 2: intermediate, 3: good, 4: excellent).

Adverse Events

Not disclosed

Study Author Conclusions

In conclusion, a single oral dose preoperative administration of 1 g TXA is shown to be effective in reducing blood loss during rhinoplasty. This method can be considered an alternative or supplementary technique for reducing blood loss in patients who are going to have surgeries.

InpharmD Researcher Critique

All patients were operated on by the same surgical team and the same anesthetic techniques.

This is a small-size study conducted in Iran; clinical applicability may be limited. The postoperative oozing (concealed blood loss) was not measured due to the confined surgical field. Present findings are limited in scope to rhinoplastic surgery only. 



References:

Eftekharian HR, Rajabzadeh Z. The efficacy of preoperative oral tranexamic acid on intraoperative bleeding during rhinoplasty. J Craniofac Surg. 2016;27(1):97-100. doi:10.1097/SCS.0000000000002273

 

Efficacy of different doses and timing of tranexamic acid in major orthopedic surgeries: a randomized trial

Design

Randomized, controlled trial

N= 200

Objective

 To compare four different dosing regimens of tranexamic acid in the reduction of blood loss intraoperatively and in the first 24 hours of the postoperative period

Study Groups

Group P (n= 40)

Group L (n= 40)

Group LM (n= 40)

Group H (n= 40)

Group HM (n= 40)

Inclusion Criteria

 Underwent major hip and femur surgeries, age 18 to 70 years, American Society of Anesthesiologists (ASA) physical status I and II

Exclusion Criteria

Undergoing revision surgeries, allergic to tranexamic acid or heparin, patients with altered coagulation profile, anemia with Hemoglobin (Hb) < 10gm.%, renal and liver dysfunction, pregnant and breastfeeding women, previous deep vein thrombosis or any thrombotic complications

Methods

Patients were randomly assigned to one of five groups:

Group L (low-dose bolus)

Group LM (low-dose bolus and infusion)

Group H (high-dose bolus)

Group HM (high-dose bolus and infusion)

Group P (placebo)

The tranexamic acid or normal saline was loaded into 50 mL solutions for both the bolus and maintenance infusion, with the placebo group receiving only normal saline. The anesthesiologist administering the solutions was blinded to the group assignment. General anesthesia and patient-controlled analgesia were standardized for all patients.

Duration

 24 hours postoperative

Outcome Measures

 Intraoperative and postoperative blood loss, mean transfusion requirements of red blood cells

Baseline Characteristics

   Group P (n= 40)

Group L (n= 40)

 Group LM (n= 40) Group H (n= 40) Group HM (n= 40)  

Age, years

 51.15 53.7 52.8 53.32 51  

Female

15 14 18 20 19  

Weight, kg

 58.8 57.3 59.25 57.7 59.6  

Duration of surgery, minutes

 151.25 148.25 135.8 161.1 139.7  

Preoperative hemoglobin

Postoperative day 4 hemoglobin

11.19

10.59

11.6

10.86

11.7

10.84

11.52

10.7

11.4

10.4

  

Type of surgery

Spine instrumentation

Total hip replacement

Femur fracture fixation

 

45%

22.5%

32.5%

 

40%

25%

35%

 

47.5%

17.5%

42.5%

 

55%

17.5%

27.5%

 

50%

22.5%

27.5%

  

Results

Endpoint

 Group P (n= 40) Group L (n= 40)

Group LM (n= 40)

 Group H (n= 40)

Group HM (n= 40)

p-Value

Intraoperative blood loss, mL

 440 412.5 290 332.5 240.7 < 0.001

Postoperative blood loss, mL

 80 89.88 56.7 77.9 46.7 0.001

Mean transfusion requirements, red blood cell packs

 31 (77.5%) 27 (67.5%) 9 (22.5%) 17 (42.5%) 9 (22.5%) 0.001

Adverse Events

 Thrombotic complications did not occur within the study and up to 6 weeks of follow-up.

Study Author Conclusions

Tranexamic acid was effective in reducing perioperative blood loss and transfusion requirements in major orthopedic surgeries. The reduction was significant when maintenance infusion was used along with a bolus dose. There was no added benefit when higher doses were used. Hence, we recommend a bolus dose of 10 mg kg−1 with a maintenance infusion of 1 mg kg−1 h−1 until the end of surgery. The thrombotic complications were not encountered in our study.

InpharmD Researcher Critique

The accuracy of blood loss estimation may not have been precise, as it relied on measuring the weight of gauzes/pads, suction bottle collection, and clinical assessment, though blood transfusion was guided by hourly hematocrit measurement which can be affected by hemodilution. The study included three different major orthopedic procedures performed by three different surgeons, which could have varying blood loss profiles, though there was no statistical difference in the surgery types between the groups.



References:

Saravanan R, Venkatraman R, Karthik K, Pushparani A. Eficácia de diferentes doses e esquemas de administração de ácido tranexâmico em cirurgias ortopédicas de grande porte: estudo randomizado [Efficacy of different doses and timing of tranexamic acid in major orthopedic surgeries: a randomized trial]. Braz J Anesthesiol. 2020;70(4):311-317. doi:10.1016/j.bjan.2020.03.013