Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study

Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study

THEKNE-02361; No of Pages 7 The Knee xxx (2016) xxx–xxx Contents lists available at ScienceDirect The Knee Optimizing effectivity of tranexamic aci...

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THEKNE-02361; No of Pages 7 The Knee xxx (2016) xxx–xxx

Contents lists available at ScienceDirect

The Knee

Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study Rajesh N. Maniar a,⁎, Tushar Singhi b, Aniket Patil c, Gaurav Kumar d, Parul Maniar e, Jaivardhan Singh f a

Lilavati Hospital, A-791, Bandra Reclamation, Bandra (W), Mumbai Pin-400050, India Department of Orthopedics, Padamshree D Y Patil Medical College, Sector 7, Nerul, Navi Mumbai 400706, India c Orthopaedic Department, Bharati Vidyapeeth Deemed University, Medical College and Hospital, Pune 4111043, India d Jhansi Orthopedic Hospital, Jhansi 284128, Uttar Pradesh, India e 51-B, Nook Apartment, S.V. Road, North Avenue Junction, Santacruz (W), Mumbai Pin-400054, India f Agrawal Ramakrishna Care Hospital, Raipur, Chattisgarh 492001, India b

a r t i c l e

i n f o

Article history: Received 11 July 2015 Received in revised form 10 October 2016 Accepted 20 October 2016 Available online xxxx Keywords: Bilateral knee arthroplasty Tranexamic acid Regimen Blood conservation

a b s t r a c t Introduction: Tranexamic acid (TEA) is used in reducing surgical blood loss. Literature shows no optimal regimen recommended for Bilateral Total Knee Arthroplasty (TKA). We evaluated three TEA regimens differing in dosage, timing and mode of administration in bilateral TKA to identify the most effective regimen to reduce blood loss. Methods: We prospectively studied three TEA regimens (25 patients each) as follows: (1) two intraoperative, intravenous doses (IOIO), (2) two intraoperative local applications (LALA), and (3) one preoperative plus two intraoperative, intravenous doses (POIOIO). Two independent parameters of drain loss and total blood loss, calculated by the hemoglobin balance method were statistically evaluated. Results: Mean drain loss was least (412.9 ml) in the POIOIO group, greatest (607.2 ml) in the IOIO group and LALA group in between (579.4 ml), with a statistically significant difference among them (p = 0.0022). On paired evaluation, the drain loss in the POIOIO group was significantly less as compared to the other two groups, whereas the difference between IOIO and LALA was not significant. Mean total blood loss was least in the POIOIO group (1207 ml) and greatest in LALA group (1270 ml). The difference among the groups was not statistically significant (p = 0.80). There was no incidence of any thromboembolic phenomenon. On correlation with our study on Most Effective Regimen in Unilateral TKA, both results were found to substantiate each other. © 2016 Elsevier B.V. All rights reserved.

1. Introduction Simultaneous bilateral total knee arthroplasty (TKA) is associated with greater blood loss and greater requirement of blood transfusions compared to unilateral TKA. Blood loss in bilateral TKA is estimated to be between 1000 ml to 3400 ml [1] as compared to 800 to 1800 ml in unilateral TKA [2,3,4,5,6].

⁎ Corresponding author. E-mail addresses: [email protected] (R.N. Maniar), [email protected] (T. Singhi), [email protected] (A. Patil), [email protected] (G. Kumar), [email protected] (P. Maniar), [email protected] (J. Singh).

http://dx.doi.org/10.1016/j.knee.2016.10.014 0968-0160/© 2016 Elsevier B.V. All rights reserved.

Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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R.N. Maniar et al. / The Knee xxx (2016) xxx–xxx

Tranexamic acid (TEA) is a synthetic analog of the amino acid lysine which inhibits fibrinolysis locally without any effect on the fibrinolysis in the plasma from peripheral venous circulation [7]. A previous study established the need for a therapeutic plasma concentration of 10 ng/ml for TEA and an 80% reduction in the activity of plasminogen activator for adequate suppression of fibrinolysis in tissues [8]. An intravenous dose of 10 mg/kg of TEA maintains such a plasma concentration for approximately three hours [8]. Evidence suggests that intravenous TEA reduces surgical blood loss (by 40 to 50%) and the requirement of blood transfusions [9]. Topical application of TEA has also been shown to be very effective [10]. Multiple previous studies have shown a reduction in blood loss and post-operative transfusion requirement with the use of TEA in patients undergoing unilateral TKA [11,12]. In our previous study on use of TEA in unilateral TKA, we have concluded that a regimen containing one pre-operative dose before tourniquet inflation, one intra-operative dose before tourniquet deflation and a post-operative dose (POIOPO), three hours after the second dose is the most effective regimen [13]. In patients undergoing simultaneous bilateral TKA, there is no ideal regimen of TEA recommended in literature. We started using TEA in bilateral TKA in July 2010 and observed a dramatic reduction in blood loss which prompted us to undertake this study. The aims of this study were, (1) to identify the most effective TEA regimen in bilateral TKA for reducing blood loss. Outcome parameters of drain collection and total blood loss by Hemoglobin Balance Method (Nadler's formula) [14,15] were estimated, (2) to compare the incidence of post-operative thromboembolic events among different regimens of TEA, and (3) to correlate with results of regimens evaluated in our Unilateral TKA study. 2. Patients and methods The study was approved by the (Lilavati hospital and research centre Ethics Committee). The study was conducted from August 2010 to April 2013. From August 2010, we prospectively assessed 97 consecutive patients with the diagnosis of bilateral osteoarthritis who were scheduled to have simultaneous bilateral TKA for inclusion in our study. We assumed a difference of 300 ml of total blood loss between groups to be clinically significant since this would equate with need for one unit of blood transfusion. Considering a power of 80% at a significance level of five percent, Stata 8.2 software (Stata Corp, College Station, TX, USA) gave a sample size of 24 per group, which we rounded to 25. The exclusion criteria were, (1) a known allergy to TEA, (2) preoperative hepatic or renal dysfunction, (3) serious cardiac or respiratory disease, (4) congenital or acquired coagulopathy, (5) deranged coagulation profile (platelet count, prothrombin time, partial thromboplastin time, and international normalized ratio) and (6) history of thromboembolic disease. Patients taking antiplatelet agents were asked to stop them at least seven days before surgery. Of these 97 evaluated patients, eight had to be excluded because antiplatelet agents were not stopped seven days prior to surgery and six other patients declined to participate (Figure 1). The selected patients were randomized into three regimen groups as follows: (1) two intra-operative IV doses (IOIO): first intra-operative dose of 10 mg/kg, 15 min before deflation of tourniquet on the first side, and second intra-operative dose of 10 mg/kg 15 min before deflation of tourniquet on the second side; (2) two intra-operative local applications (LALA): three grams of TEA diluted in 100 ml normal saline applied locally to the whole synovium after cementing the implant and before tourniquet release on first side, and also three grams diluted in

Figure 1. Flow diagram indicating the number of patients assessed and included at each stage of the trial.

Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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100 ml normal saline applied locally to the whole synovium after cementing the implant and before tourniquet release on the second side. At least five minutes of contact time was allowed before the tourniquet deflation. (3) One pre-operative plus two intra-operative doses (POIOIO): 10 mg/kg, 20 min before tourniquet inflation on the first side as the preoperative dose, 10 mg/kg before tourniquet deflation on the first side as the first intra-operative dose and 10 mg/kg, three hours after the second dose as the second intra-operative dose. In view of the established efficacy of TEA in reducing surgical blood loss, it was decided that patients undergoing TKA should not be deprived of the benefit of TEA and subjected to more blood loss. Thus, a control group with no TEA administered was not considered. The randomization was done on the day of surgery. An anesthetic resident, who was not an observer for the study parameters, randomly picked an envelope from a set of 75 envelopes (25 envelopes for each group). The randomization was conveyed to the senior anesthetist. During surgery, eight patients (four each in IOIO and POIOIO groups) failed to receive the allocated TEA regimen as per protocol timing and thus were withdrawn from the study (Figure 1). For each of them, a new envelope of the same regimen was added to the box and mixed. Thus, 83 patients were randomized to achieve our target sample size of 75 patients (25 in each study group). The general demographics (age, sex, BMI), comorbidities (diabetes mellitus, thyroid status and hypertension), peripheral blood volume by Nadler's formulae [14], tourniquet time and pressure, and total surgical time were recorded for all patients. All operations were performed by the senior author (RNM) using computer navigation and the PFC Sigma series of total knee prostheses (DePuy Orthopedics Inc., Warsaw, IN, USA). The tourniquet was inflated to between 270 and 320 mm Hg for the first side after exsanguination with an Esmarch bandage. A midline skin incision, with a midvastus arthrotomy was undertaken for all patients. Cement with gentamicin was used for fixation of the prosthesis. The tourniquet was deflated after cementing the implant and hemostasis was achieved by electrocoagulation. The final polyethylene liner was then inserted followed by layered closure of the wound. There was an interval of approximately 40 to 50 min between tourniquet deflation and conclusion of surgery. One intra-articular drain and one subcutaneous drain were placed and connected to vacuum drain bottles. The deep drain was blocked for two hours after the procedure. After doing dressing of the first side, a new drape was applied for the second side and surgery of the second knee was started and done in the same manner as the first side. The day of operation was considered as Day 0. For all patients who underwent surgery between seven am and 12 noon, Day one drains were recorded at eight am; and for all patients who underwent surgery between 12 noon and five PM, they were recorded at 12 noon. Thus, there was a variable duration ranging from 20 to 24 h for Day one drain collection, but this was distributed among the groups as the patients were randomized. The Day 2 drains were recorded at the same time, i.e., eight am for all patients. All patients began mobilization and flexion exercises on Day two after surgery. Our protocol for postoperative rehabilitation was the same for all patients. Each patient was made to stand on Day two after surgery and discharged on Day six after surgery. The blood hemoglobin concentration was determined preoperatively and on Days one, two and five after surgery for all patients. Our protocol for giving blood transfusions, as per senior authors' preference was as follows: (1) patients whose hemoglobin was less than 8.5 g/dl; (2) all patients with cardiac disorders whose hemoglobin was less than 10 g/dl; and (3) patients whose hemoglobin was above 8.5 g/dl but who had symptoms related to anemia such as tachycardia, tachypnea, or decreased exercise tolerance. There is wide variability in the recommended transfusion trigger in literature. A hemoglobin of seven to eight grams per deciliter in young fit patients and a hemoglobin of b 10 g/dl in cardiac patients is generally regarded as the transfusion trigger in TKA in addition to clinical symptoms of anemia [16,17,18,19]. We recorded blood transfusions for quantity and determined the hemoglobin concentration of each transfused unit. We had advised blood transfusions to patients based on the protocol mentioned above, but not all patients consented to transfusion. Some of them refused to receive blood donated by an unknown person due to social, religious or cultural reasons. Because of this, there was variability between the number of patients who were advised transfusions based on our protocol and the number who received transfusions. Although recorded, we did not include transfusion requirement as a parameter for comparison. However the Total Blood Loss formula [14,15] that we used, included the amount of blood transfused and its hemoglobin content into the calculation. We studied two independent parameters to determine the efficacy of TEA on reducing blood loss. One was the drain loss which was the sum of the drain collection of both sides on Day one (Day one drain loss) and on Day two (Day two drain loss). To quantify the efficacy of different regimens on drain loss we have calculated and analyzed Day one and two drain losses as well as the first and second surgical side drain losses separately. The other parameter was the total blood loss calculated by the hemoglobin balance method [14,15], which involved measuring hemoglobin levels at several stages. This calculation gave better estimation of the combined external loss, i.e. intra-operative loss, drain loss and the internal (hidden) blood loss. The patient, the floor nurse who recorded the drain collections, and the hospital laboratory technician who estimated hemoglobin were blinded to the regimen received by the patient. Local application of TEA had to occur during surgery; therefore the senior author who was the operating surgeon could not have been blinded to the regimen being given to the patient. For calculation of the total blood loss by the hemoglobin balance method, the patient's blood volume was first calculated using the formula of Nadler et al. [14] as follows: patient's blood volume = (k1 ∗ height3 [meters]) + (k2 ∗ weight [kilograms]) + k3, where k1 = 0.3669, k2 = 0.03219, and k3 = 0.6041 for men and k1 = 0.3561, k2 = 0.03308, and k3 = 0.1833 for women. The loss of hemoglobin then was estimated according to the following formula: Hbloss = patient's blood volume ∗ (Hbi − Hbe) ∗ 0.001 + Hbt, where Hbloss (grams) was the amount of hemoglobin lost up to Day 5 after surgery, Hbi (grams/l) was the hemoglobin concentration before surgery, Hbe (grams/l) was the hemoglobin concentration on the fifth day after surgery, and Hbt (grams) was the amount of hemoglobin transfused [15]. From these, the total blood loss in milliliters was calculated as follows: total blood loss = 1000 ∗ Hbloss / Hbi [15]. Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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Protocol for deep vein thrombosis (DVT) prophylaxis was as follows: (1) ankle and foot movement exercises were started as soon the anesthesia effect wore off; (2) low molecular-weight heparin (Enoxaparin sodium; 40 mg daily subcutaneously) was given to all patients beginning on Day one and continued until the time of discharge; and (3) below-knee compression stockings were given to all patients. The patients were monitored for occurrence of any complications, particularly DVT and thromboembolism during the hospital stay and for three months postoperatively. We analyzed sex differences among the groups using the chi-square test. We analyzed group differences in the study parameters (total drain loss, Day one and Day two drain losses, first and second surgical side drain losses, total blood loss) and, demographic and operative parameters (age, BMI, patient's blood volume, tourniquet time, and pressure) using ANOVA. If a significant difference between groups was found by ANOVA then paired differences were examined by Scheffe's test. The significance level used for all tests was p ≤ 0.05. Analyses were performed using Stata® 8.2 software. 3. Results There were no differences in the general demographics among the groups (Table 1). Total surgical time, tourniquet time and pressure among the groups were also comparable (Table 2). On comparison of drain loss in the three TEA regimen groups, it was seen that the mean drain loss was least (412.9 ml) in the POIOIO group, greatest (607.2 ml) in the IOIO group and LALA group in between (579.4 ml) with a statistically significant difference among them (p = 0.0022) (Table 3). On paired evaluation, the drain

Table 1 Comparison of baseline demographics between groups. Variable

IOIO

LALA

POIOIO

Number of patients

25

25

25

4 (16.0)

2 (8.0)

3 (12.0)

21 (84.0)

23 (92.0)

22 (88.0)

65.9 (6.2) [62.8, 69.0]

62.2 (7.1) [59.2, 69.3]

65.5 (8.9) [62.4, 68.6]

28.9 (4.5) [27.2, 30.6]

30.3 (3.9) [28.6, 32.0]

31.5 (4.5) [29.8, 33.2]

3900.5 (523.5) [3714.0, 4087.1]

3847.9 (382.2) [3661.4, 4034.5]

3933.3 (489.9) [3746.1, 4119.3]

128.6 (10.7)

127.4 (8.3)

123 (11.9)

14 (56.0)

12 (48.0)

16 (64.0)

11 (44.0)

13 (52.0)

9 (36.0)

6 (24.0)

3 (12.0)

8 (32.0)

19 (76.0)

22 (88.0)

17 (68.0)

3 (12.0)

4 (16.0)

6 (24.0)

22 (88.0)

21 (84.0)

19 (76.0)

Sex

Male N (%) Female N (%)

Age (years) Mean (SD) [95% CI] Body mass index Mean (SD) [95% CI] Peripheral blood volume (ml) Mean (SD) [95% CI] Pre op Hb (g/l) Mean (SD) Hypertension Yes N (%) No N (%) Diabetes Yes N (%) No N (%) Thyroid Yes N (%) No N (%)

p value 0.90⁎⁎

0.17⁎

0.11⁎

0.81⁎

0.14⁎

0.56#

0.27#

0.65#

IOIO = two intra-operative dosages; LALA = two local applications; POIOIO = one pre-operative with two intra-operative dosages. ⁎⁎ Using chi-square test, significant if p ≤ 0.05. ⁎ Using ANOVA, significant if p ≤ 0.05. # Using Fisher's exact.

Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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Table 2 Comparison of surgical time, tourniquet time and pressure among groups. Variable

IOIO

LALA

POIOIO

Number of patients

25

25

25

74.6 (14.2) [70.1, 79.1] 73.4 (8.0) [69.8, 76.9] 283.2 (18.9) [277.7, 288.8] 287.2 (18.1) [281.4, 293.0] 131.8 (11.4) 137.8 (15.9)

76.6 (10.9) [72.1, 81.1] 72.3 (8.4) [68.8, 75.9] 285.2 (11.9) [279.7, 290.7] 288.8 (14.2) [282.9, 294.6] 139.1 (12.5) 136.4 (15.2)

80.1 (9.4) [75.6, 84.6] 77.6 (8.9) [74.1, 81.1] 288.4 (9.9) [282.9, 293.9] 289.2 (9.5) [283.3, 295.0] 138.2 (14.7) 131.1 (15.6)

Tourniquet time in minutes Mean (SD) [95% CI]

Side-1

Tourniquet pressure in mm of Hg Mean (SD) [95% CI]

Side-1

Surgical time in minutes Mean (SD)

Side-1

Side-2

Side-2

Side-2

p value⁎ 0.25

0.07

0.43

0.87

0.29 0.51

IOIO = two intra-operative dosages; LALA = two local applications; POIOIO = one pre-operative with two intra-operative dosages. ⁎ Using ANOVA for comparison among groups; significant if p ≤ 0.05.

loss in the POIOIO group was significantly less as compared to the other two groups (Table 3), whereas the difference between IOIO and LALA was not significant. Results thus suggest that the POIOIO regimen was significantly more effective in reducing drain loss compared to IOIO and LALA regimens. On evaluating the drain loss for Day one and Day two separately (Table 4), we observed that Day one drain loss differed considerably among the three regimens as against Day two drain loss which was similar in all three regimens. On comparison of mean total blood loss in three TEA groups, it was seen that the mean total blood loss was least in the POIOIO group (1207 ml) and greatest in LALA group (1270 ml) and the difference among the groups was not statistically significant (p = 0.80) (Table 5). Results thus suggest that the POIOIO regimen showed least total blood loss compared to IOIO and LALA regimens but the difference was not statistically significant. The day of ambulation and the day of discharge were the same in all patients. There were five patients (two in control group, two in POIOIO group, one in IOIO group), where clinically DVT was suspected and venous color Doppler study was carried out. No patient was detected to have DVT. 4. Discussion The aims of this study were, (1) to identify the most effective regimen in bilateral TKA for reducing blood loss, (2) to compare the incidence of post-operative thromboembolic events among different regimens of TEA, and (3) to correlate results with our Unilateral TKA study. The study had some limitations. Our sample size calculation was based on a difference of 300 ml in total blood loss, as there is no previous study to help calculate differences between different treatment regimens. This may have been rather large to delineate differences between regimens, but we feel that the current study will provide information for calculating sample size for any future study. Secondly, we have not studied a control group, where TEA was not administered. This is because TEA has established its efficacy in significantly reducing surgical blood loss and we did not think it right to subject any patient to greater blood loss by depriving him of the benefit of TEA. Thirdly, no cost–benefit analysis was done for this study. Lastly, we did not record patients' ASA grade and whether patients were on any iron supplements, which could have some bearing on blood loss or on hemoglobin Table 3 Comparison of drain loss among groups. Variable Drain loss (ml) Mean (SD) [95% CI] Difference in drain loss between groups in ml (p value‡)

IOIO

LALA

POIOIO

607.2 (196.5) [501.4, 713.1] −27.8 (1.00) −194.4 (0.004#)

579.4 (208.3) [473.6, 685.2]

412.9 (205.8) [307.1, 518.7]

p value⁎ 0.0022#

LALA POIOIO

−166.6 (0.015#)

IOIO = two intra-operative dosages; LALA = two local applications; POIOIO = one pre-operative with two intra-operative dosages. ⁎ Using ANOVA for comparisons among groups; significant if p ≤ 0.05. ‡ Using Scheffe's test for paired comparisons; significant if p ≤ 0.05 (value adjusted to be significant at b0.05). # Significant values.

Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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R.N. Maniar et al. / The Knee xxx (2016) xxx–xxx

Table 4 Comparison of Day one and Day two drain losses among groups. Variable

IOIO

LALA

POIOIO

Number of patients

25

25

25

317.7 (109.5) [256.1, 379.3] 0.84 (1.0) −111.8 (0.002)$

318.5 (131.9) [256.9, 380.1]

205.9 (88.1) [144.3, 267.5]

Day one drain loss in ml Mean (SD) [95% CI] Difference in drain loss in ml (p value‡)

0.0005$

LALA POIOIO

Day two drain loss (ml) Mean (SD) [95% CI] Difference in drain loss in ml (p value‡)

p value⁎

−112.6 (0.002)$ 0.092

LALA POIOIO

290.4 (134.6) [223.8, 356.9] −29.5 (1.0) −83.4 (0.09)

260.9 (123.07) [194.4, 327.5]

207 (145.4) [140.5, 273.5]

−53.9 (0.484)

IOIO = two intra-operative dosages; LALA = two local applications; POIOIO = one pre-operative with two intra-operative dosages. ⁎ Using ANOVA for comparisons among groups; significant if p ≤ 0.05. ‡ Using Scheffe's test for paired comparisons; significant if p ≤ 0.05 (value adjusted for significance to be shown at b0.05). $ Significant differences.

levels in the postoperative period. However, since it is a randomized study, we expect these factors to be distributed among the groups. Both our study parameters of drain loss and total blood loss showed maximum reduction with POIOIO regimen compared to IOIO and LALA regimens, with the difference in drain loss being statistically significant. An intravenous dose of 10 mg/kg of TEA maintains therapeutic plasma concentration for approximately three hours [8]. Fibrinolysis is a cascade reaction, so it would be best to inhibit it early [20]. Optimization of the timing of administration to cover the fibrinolytic cascade is key to achieving optimal reduction in blood loss. In unilateral TKA study [13], we had identified POIOPO (pre/intra/post-operative) regimen as the most effective regimen. The POIOIO regimen in this Bilateral TKA study involved an intra-operative dose during first TKA which effectively acted as pre-operative dose for second TKA. Similarly the intra-operative dose during second TKA effectively acted as post-operative dose for first TKA. Considering this information in light of our Unilateral TKA study [13], the results substantiate each other convincingly. Kim et al. [21] in their Bilateral TKA study reported reduced need for blood transfusion with their regimen of two intraoperative doses of TEA (IOIO) as compared to control. However, they did not study any preoperative dose regimen, which has been shown as most effective in earlier studies [13,20,22]. Hegde et al. [23] compared two regimens — one using two IV doses (IOIO) and the other using two local applications (LALA) against a control (placebo) group. They reported equally significant reduction in blood loss with both the regimens, with no difference between their effectivity, similar to our study. However they compared Hb levels and the need for transfusions as study parameters. Our study has used the Nadler's formula, calculating blood loss by the hemoglobin balance method, which is a more accurate estimation [14,15]. In addition, the present study revealed that Day one drain loss was a more significantly reduced parameter compared to Day two drain loss. This indicates that TEA is most effective on the first day following surgery. There were no thromboembolic events in any of the TEA groups, this is in conformity with earlier studies regarding the safety profile of TEA in TKA [4,12,15].

5. Conclusion We conclude that, of the three regimens studied, the three dose-POIOIO regimen was significantly more effective in bilateral TKA. TEA proved to be safe with no thromboembolic occurrence with its use. Results are convincingly affirmative with results of our Unilateral TKA study. Table 5 Comparison of total blood loss among groups. Variable Total blood loss (in ml) (SD) [95% CI]



IOIO

LALA

POIOIO

p value⁎

1244.6 (228.8) [1095.9, 1393.3]

1270.02 (384.2) [1121.3, 1418.7]

1207.8 (380.7) [1059.1, 1356.6]

0.80

IOIO = two intra-operative dosages; LALA = two local applications; POIOIO = one pre-operative with two intra-operative dosages. ⁎ Using ANOVA for comparisons among groups. † Values are expressed as mean, with SD in parentheses.

Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014

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Acknowledgment We thank (Dr. Arun Nanivadekar) MD MSc, Medical Research Consultant, (Lilavati Hospital and Research Centre, A-791, Bandra Reclamation, Bandra (W), Mumbai, India.Pin-400050), for his assistance with statistical analysis of our data.

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Please cite this article as: Maniar RN, et al, Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty — A prospective randomized controlled study, Knee (2016), http://dx.doi.org/10.1016/j.knee.2016.10.014