International Journal of Research in Orthopaedics

Kamat SG et al. Int J Res Orthop. 2021 Mar;7(2):308-318

http://www.ijoro.org

Original Research Article

DOI: https://dx.doi.org/10.18203/issn.2455-4510.IntJResOrthop20210624

Retrospective comparative study of IV+ local tranexamic acid versus IV tranexamic acid only in primary total knee replacement

Sanil G. Kamat1*, Rohan Dessai2

1Department of Orthopaedics, The Princess Alexandra Hospital NHS trust, United Kingdom

2Department of Orthopaedics, Manipal Hospital, Goa, India

Received: 22 November 2020

Revised: 05 January 2021

Accepted: 06 January 2021

*Correspondence:

Dr. Sanil G Kamat,

E-mail: kamat.sanil@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: The study is to compare the immediate post-operative outcomes with use of intravenous (IV) tranexamic acid (TXA) versus IV and local TXA combination in primary unilateral total knee arthroplasty. Study comprised of 72 cases of tricompartmental knee primary osteoarthritis who have undergone unilateral total knee arthroplasty at Manipal Hospital, Goa from January 2016 to December 2018. The observations for each group was analysed and post op blood loss in drain, fall of haemoglobin levels and need of blood transfusion was recorded. The results were statistically compared. The mean blood loss fall in HB levels and need of blood transfusions revealed statistically significant differences.

Methods: Total 72 patients diagnosed with primary tricompartmental osteoarthritis were divided into two groups retrospectively. Group 1 (IV only): 1 gm IV Tranexamic acid bolus 10 min before deflating the tourniquet. Group 2 (IV + Local): 1 gm IV Tranexamic acid bolus 10 min before deflating the tourniquet and 1 gm Tranexamic Acid in 50 ml saline locally at the time of closure.

Results: It was observed that higher post op blood loss, higher fall in haemoglobin (HB) levels and higher requirement of blood transfusions were associated with group 1 as compared to 2.

Conclusions: The study inferred that the combination of local and systemic tranexamic acid was superior than systemic administration alone with lower post op blood loss, lower rates of blood transfusion and lower fall in haemoglobin levels without any added complications.

Keywords: Total knee replacement, Tranexamic acid, Haemoglobin, Blood transfusion

INTRODUCTION

Total knee replacement is the only surgical option currently available in case of well-established tricompartmental osteoarthritis. Intra and postoperative bleeding remains one of the main concerns in total knee arthroplasty (TKA), with blood loss ranging between 1000±500 ml.1 The use of a pneumatic tourniquet ensures a dry surgical field and minimal intraoperative bleeding, but it augments fibrinolysis stimulated by surgical trauma.2-7 This activation of the fibrinolytic system might lead to high postoperative blood loss . Different methods to reduce perioperative blood loss have been studied, such as perioperative blood donation, perioperative red cell salvage, deliberate hypotension, and use of recombinant human erythropoietin. Furthermore, perioperative transfusions add to the costs of the treatment and the risks (of infection, allergic reaction and disease transmission, for example) to the patient.8

In recent times, pharmacological approaches are attracting a lot of attention. As hyperfibrinolysis is considered one of the major causes of postoperative bleeding after TKA surgery, antifibrinolytic drugs have been proposed, including aprotin, aminocaproic acid, and tranexamic acid (TXA).

Tranexamic acid9-12

Tranexamic acid is used in orthopaedic surgery to reduce blood loss, to the extent of reducing or altogether abolish-ing the need for perioperative blood collection. It is of proven value in clearing the field of surgery and reducing blood loss when given before or after surgery. Drain and number of transfusions are reduced.

Tranexamic acid is a synthetic analogy of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, prevent-ing fibrin degradation and preserving the framework of fibrin's matrix structure. Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid. TXA inhibits fibrin cleavage, thus reduc-ing the risk of haemorrhage. TXA also directly inhibits the activity of plasmin with weak potency (IC50=87 mM) and it can block the active-site of urokinase plasminogen activator (uPA) with high specificity (Ki=2 mM) among all the serine proteases. Plasma protein binding of 3%. Low hepatic metabolism and 95% renal clearance and half-life approximately 2.3 hours.

The aim of the present study was to compare the efficacy of systemic versus systemic plus local administration of TXA in reducing blood loss after TKA.

METHODS

Source of data

The retrospective study was conducted in a tertiary institute by collecting data of 72 cases of tricompartmental knee primary osteoarthritis who have undergone unilateral total knee arthroplasty at Manipal Hospital, Goa from January 2016 to December 2018.

The data collected from medical record department of Manipal Hospital. Data was statistically analysed to reach a conclusion. Analysis is descriptive with limitation as patients were analysed from the time of surgery till the post operative day 3. All cases operated by two surgeons with same techniques and same anaesthesia protocol.

Study design

This is a comparative retrospective study in which patients were admitted and operated at Manipal Hospital from January 2016 to December 2018.The comparison in terms of: post-operative blood loss, fall in haemoglobin level post operative, post operative blood transfusion rate.

All patients underwent TKR by cemented, medial para-patellar, and posterior cruciate ligament substituting method. Tourniquet were used in all patient which was inflated before the incision and was deflated at the time of closure. Tablet Rivaroxaban 10 mg OD started for all patients from POD1 for prophylaxis against DVT. All patients received rehabilitation after the surgery including pain management, exercises for Range of Motion (ROM) re-gaining and muscular strength enhancement. The exercises majorly included active ankle pumping for deep venous thrombosis prevention and oedema control, active and active-assisted ROM exercises of knee flexion and extension, strengthening knee joint musculature with special emphasis on knee extensors by isometric method progressing to isotonic exercise and gait education with walker and cane. Exercise performance was supervised by a physiotherapist.

Ethical approval

No ethical approval was required as it’s a retrospective study and patients personal details not mentioned in the study.

Software statistical package for social sciences (SPSS) version 20.0 used for statistical analysis.

Use of tranexamic acid

Group 1 (IV only)

1 gm IV Tranexamic acid bolus 10 min before deflating the tourniquet.

Group 2 (IV + Local)

1 gm IV Tranexamic acid bolus 10 min before deflating the tourniquet and 1 gm Tranexamic Acid in 50 ml saline locally at the time of closure.

Inclusion criteria

Surgically fit patients more than 50 years of age who has been diagnosed as having tri compartmental primary osteoarthritis knee.

Exclusion criteria

Known RA of knee, complicated surgeries with need for computer navigation, age less than 50 years, patients with preop Hb levels less than 10, revision TKRs, patients with contraindications to Tranexamic acid administration (a medical history of DVT or pulmonary thromboembolism, acute myocardial infarction, heart failure, heart valve stenosis, ischemic stroke, coagulopathy, allergy to TXA, severe liver or kidney disease), patient with known coagulation disorders.

RESULTS

The average post operative drain on day 1 in group 1 cases was 275.4 which was noted to be significantly higher than in group 2.

Table 1: Post-operative day1 drain collection.
Table reproduced from source PDF page 3

Furthermore, the average post op drain on day 2 in group 1 also appeared to be considerably higher than group 2 by almost 40.6 ml. In Addition to this, more number of drains were retained in group 1 patients as compared to group 2 on post operative day.

Table 2: Post-operative day2 drain collection.
Table reproduced from source PDF page 3

Also, preoperative hemoglobin levels were almost identical in both the groups, however there was a significant drop in post op hemoglobin in group 1 as compared to group 2. Lastly, higher incidences of blood transfusion was observed in group 1 but it was not statistically significant.

Table 3: Day 3 post-operative drain retention.
Table reproduced from source PDF page 3
Table 4: Preoperative hemoglobin levels.
Table reproduced from source PDF page 3
Table 5: Post-operative hemoglobin levels.
Table reproduced from source PDF page 3
Table 6: Fall in hemoglobin levels.
Table reproduced from source PDF page 3
Table 7: Blood transfusions.
Table reproduced from source PDF page 4

DISCUSSION

Perioperative blood loss is an inevitable complication of revision TKA, which could lead to anaemia. Effective blood management can minimize blood loss and transfusions such that patients achieve better results. This study demonstrated that TXA is effective in reducing total blood loss, transfusion rate and blood in the drain, without increasing the rate of complications. Furthermore far better results in terms of lesser post-operative blood loss, lesser rates of blood transfusions and lower fall of post operative Hb was evident when Systemic Tranexamic acid was coupled with local infusion.

Table 8: Summary of meta-analyses on the efficacy of tranexamic acid in total knee arthroplasty.
Table reproduced from source PDF page 4, part 1 of 2
Table reproduced from source PDF page 5, part 2 of 2

Abbreviations: TXA = tranexamic acid; IV = intravenous; IA = intra-articular; CI = confidence interval; MD = mean difference; SMD = standardized mean difference; RR = risk ratio; RCT = randomized controlled trial; Quasi-RCT = quasi-randomized controlled trial; PCS = prospective cohort study.

The regimen proposed in the study was based on review of literature and our experience.

It has been demonstrated via various study that TXA is effective as well as safe when given by systemic or local route.13

Levine et al., in a randomized controlled trial, demonstrated that a standard dose of 1 g IV can be used with the same efficacy as weighted doses (20 mg/kg).14 Iwai et al. demonstrated that a double IV dose of TXA produced a further reduction of postoperative blood loss in TKA compared to a single administration, especially if the doses were given preoperatively and intraoperatively.15 Similarly, Maniar et al., also in a Prospective study (RCT), demonstrated that a three-dose regimen (adding a postoperative dose) may be even more effective than single dose regimens.16

Most of the studies summarised below confirmed the effectiveness of varied doses of IV TXA in minimising post op blood loss and need for blood transfusions.

Table 9: Summary of randomized controlled trials on the efficacy of tranexamic acid in total knee arthroplasty.
Table reproduced from source PDF page 6, part 1 of 3
Table reproduced from source PDF page 7, part 2 of 3
Table reproduced from source PDF page 8, part 3 of 3

Abbreviations: TXA = tranexamic acid; TKA= total knee arthroplasty; IV= intravenous; IA= intra-articular; Hb= haemoglobin.

Although, some researchers reported a potential increased risk of thrombotic events and some cases of allergic reaction, this study however did not come across any of these complications.49 Different Authors have studied the efficacy of IA administration, proposing different doses and multiple methods of local administration (washing or through the drain). In particular, Georgiadis et al. randomized patients to two groups receiving either 2 g of TXA in 75 ml of saline or a placebo solution intraoperatively.41 The Authors demonstrated a significant reduction of total blood loss in the TXA group, without the potential complications related to IV administration. Patel et al., in a study of 89 patients who underwent a primary TKA, demonstrated that IV administration of 10 mg/kg of TXA and IA admin-istration of 2 g TXA were equally effective in reducing blood loss.37 Similarly, various recent studies have demon-strated the efficacy of IA TXA administration in reducing blood loss after TKA.

In addition to this, few recent meta-analyses showed no difference between topical and IV TXA administration, even though some authors reported conflicting results.

Very few studies have compared systemic TXA against local TXA. Jain et al. showed better results in terms of mean total blood loss, transfusion rate and haemoglobin drop, using a combined protocol compared to only IV administration.26 Similarly, Lin et al., in a study of 120 patients, demonstrated greater reductions in blood loss, haemoglobin drop, total drain amount and transfusion rate using a combined protocol compared to IA administration alone.32 Karaaslan et al. evaluated the efficacy of an association of three different methods of TXA administration in bilateral TKA: a bolus dose of 15 mg/kg 10 min before the inflation of the tourniquet, followed by IA administration of 3 g 10 min before the deflation of the tourniquet, associated with an IV infusion of 10 mg/kg/h for 3h following the surgery. The authors concluded that this method of TXA administration was effective in reducing total blood loss in bilateral TKA.30 Huang et al. compared the results of IV TXA administration (3 g) with those of a combined approach (1.5 g IA and 1.5 g IV). The Authors concluded that the two approaches were similarly effective in reducing transfusion rate and total blood loss, but the combined protocol gave better results in terms of maximum decline of haemoglobin, drainage volume, postoperative knee pain, knee swelling, length of hospital stays and short-term satisfaction.45

In view of the established efficacy of TXA in TKA irrespective of the method of administration, we conducted a preliminary retrospective study in 72 patients, divided into IV group and IA + IV group. The aim of this study was to evaluate whether one method of administration was more effective than the other. The results of the study showed marked differences in haemoglobin loss, amount of blood in the drain, and rate of transfusions between the combined protocol and systemic administration alone.

The main limitation in the study is the absence of a control group. That said, the efficacy of TXA, whether administered topically or systemically, has previously been extensively described and is widely accepted. Finally, the power of the study was certainly reduced by the small size of the sample. However, these are preliminary data, and the study will be continued, introducing a randomization procedure, to confirm the significance of the results obtained.

CONCLUSION

The study inferred that the combination of local and systemic tranexamic acid was superior than systemic administration alone with lower post op blood loss, lower rates of blood transfusion and lower fall in haemoglobin levels with-out any added complications.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the institutional ethics committee

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