European Journal of Cardiovascular Medicine

Surgery is one of the  most common causes of major blood loss. Total hip arthroplasty in adults is often associated with significant blood loss requiring transfusion due to extensive soft tissue dissection, and significant bone bleeding during reaming(1-4) . A variety of contemporary blood-conservation techniques have  been used to reduce exposure to allogeneic blood, including controlled hypotension, regional anesthesia, autologous blood transfusion, intraoperative blood salvage and administration of various intravenous (IV), intramuscular, and oral medications(5).

However, these haemostatic techniques are not applied in replacement surgeries consistently. Tranexamic acid (TXA), a synthetic antifibrinolytic agent, is one common medication that could competitively block the lysine-binding sites of plasminogen, plasmin, and the tissue plasminogen activator, thereby retard fibrinolysis and blood clot degradation(6). Antifibrinolytics have been demonstrated to reduce blood transfusion requirement during cardiac surgery, spine surgeries, and urology surgeries(7,8,9), suggesting that TXA may have a similar effect in THR. However, there are only a few studies evaluating the role of TXA in hip replacement surgery. With the inherent risks associated with blood loss and blood transfusion, a double blind randomized controlled study was undertaken to compare blood loss in patients receiving TXA and otherswho did not receive TXA.

Institutional ethical committee approval was taken for this prospective , randomised, double blind study. Written informed consent was obtained from the patients. Patients aged between 40-75 years undergoing total hip arthroplasty of ASA I and II were included. Random allocation of patients into two groups of 30 patients eachgroup II ( N = 30 )  group I ( N = 30) was done using computer-based randomization method. Patients with bleeding disorder or on anticoagulants, COPD, hepatic or renal failure were excluded. All patients were kept nil per oral overnight and administered oral tablet alprazolam 0.5 mg . On arrival to the operation theater , IV access using 18G cannula on the nondominant hand was secured. Infusion of Ringer Lactate 500 ml was started 30 minutes prior to induction. All the subjects were connected with the multipara monitor for recording SpO2, Non Invasive Blood pressure (NIBP) and heart rate (HR). Subjects were premedicated with inj. fentanyl 1 to 2 µg per kg. Preoxygenation was done with 100% O2 for 3 minutes. General anaesthesia was induced with Inj. propofol 1 to 2mg/kg I.V slowly and the end point for induction was taken as loss of eye lash reflex. Inj.Vecuronium 0.1mg/kg I.V was given and subjects were mask ventilated for 3 minutes. All the subjects were intubated with appropriate size cuffed ET tube with gentle laryngoscopy and tracheal position of the tube confirmed by end tidal carbon dioxide (EtCO2). Anesthesia was maintained with Oxygen+ Nitrous oxide + Inj.Vecuronium + 1-1.5% Isoflurane.

Group II patients received tranexamic acid 10mg/kg of body weight  mixed in 100ml normal saline shortly after induction of anaesthesia over 15 min before skin incision ,followed by infusion of 1mg/kg of body weight per hour upto closure of skin incision.Group Ipatients received placebo (100 ml of 0.9% Normal saline only) in a similar manner as Group II during the intra-operative period.Outcome measures included perioperative blood loss, amount of blood transfusion, as well as pre and postoperative hemoglobin and hematocrit levels. We determined the perioperative blood loss by measuring the volumes in the suction apparatus, estimating the swab content and collection in vacuum drain. Volume of blood collected in drain were measured and recorded at 8, 16 hours following surgery. Total amount of blood collected in the drain 24 hours following surgery was measured and charted.

Table 1:Demography And Pre-Op Investigations

Both groups were comparable with respect to demographics, pre-operative investigations and the duration of surgery.

INTRAOPERATIVE BLOOD LOSS

In group I, the intraoperative blood loss was849.00±192.8 ml which was much lesser in group II,628.05±170.21 ml and was statistically significant.(p value-0.034).

POSTOPERATIVE BLOOD LOSS

The postoperative blood loss was136.38±47.65 ml in group II, compared to275.20±64.01 ml in group I whichwas statistically significant with p value of 0.035.

TOTAL BLOOD LOSS

The total blood loss too was lesser in group II(1123.08±229.61 ml) compared to group I(768.53±225.81 ml) and was found to be statistically significant.(p value-0.045).

In group I, there was drastic fall in both Hb and haematocrit as compared to group II and it was stastically significant.

GRAPH DEPICTING FALL IN Hb

Table 2:Comparision Of Pre Operative And Post Operative Hemoglobin And Packed Cell Volume

Table 3: Packed Red Blood Cells Transfused

The number of packed red blood cells received by patients in Group I was 35 and in Group II was 15 and wasstatistically significant(p value-0.032).

In the present study, 80 patients were randomly allocated to control group and tranexamic acid group. Both groups were comparable in the mean age, bodyweight, pre-operative haemoglobin, hematocrit values,INR and the duration of the surgery. The technique of anaesthesia was standardized in both the groups. Contributing factors like coagulation profile and mean arterial blood pressure that could alter blood loss were monitored. Hypotensive anaesthesia was not used in both the groups.

In this study, we found that the mean intra-operative blood loss was less in the tranexamic acid group compared to the control group(p value-0.034),the amount of blood in the drains post-operatively was less in tranexamic acid group(p value-0.035) and the total blood loss(intra-operative plus post-operative) was consequently less in tranexamic acid group. (32% reduction in total blood loss with p value-0.045).

The blood transfusions received in both the groups was statistically significant(p value-0.032). The number of units of PRBCs’ received in control group and tranexamic acid group was 35 and 15 respectively.

These results were consistent with studies done by M.A.Claeys et al(10).M.A.Claeyset al  reported that postoperative blood loss up to 24 hrs, and total blood loss were significantly less in the TA group: 352 vs 524 ml (p value- 0.013), and 801 vs 1038 ml (p value-  0.013), respectively. Packed red blood cell transfusion requirements were significantly lower in the TA group (1/20 patients, total 2 units) compared to the placebo group (6/20 patients, total 13 units). Duquenne et al.(11), Ekback et al. (12) and Ido et al. (13) have reported results similar to ours. The prophylactic administration of tranexamic acid signicantly reduced the post- operative (Ido et al. (13)) and total blood losses (Ekback et al. (12)). This has also been shown in total knee arthroplasties (Benoni et al.(14), Hiippala et al.(15), Jansen et al.(16)). In knee arthroplasty, tranexamic acid also reduced the number of blood transfusions.

Henrik Husted et al(17),reported that Tranexamic acid  significantly reduced blood loss and blood transfusions in primary total hip arthroplasty  following  a prospective randomized double-blind study in 40 patients.Wong J et al (18), Elwatidy S et al(19), and Wang Q et al(20), reported that total estimated and calculated perioperative blood loss was approximately 25% and 30% lower in patients given TXA versus placebo (1592 +/- 1315 mL vs 2138 +/- 1607 mL, P = 0.026; 3079 +/- 2558 vs 4363 +/- 3030, P = 0.017), respectively  in adult patients having spinal fusion surgery.Elwatidy S et al (19) reported that patients who received tranexamic acid had 49% reduction of blood loss (P < 0.007) compared to control group in spine surgeries.Wang Q et al(20) reported postoperative blood loss was significantly lower than that in the control group (13.0 %)  in posterior approach lumbar surgery for degenerative lumbar instability with stenosis.

The difference in the pre and post-operative haemoglobin and hematocrit values of patients in tranexamic acid group compared to control group was statistically significant (p value- 0.044 and 0.034 respectively). These results were consistent with studies done by Endres et al(21) and Elwatidy et al(19) in which the difference in pre and postoperative hemoglobin  and hematocrit values were statistically significant in tranexamic acid group compared to the control group.

The major concern surrounding the use of TXA and other antifibrinolytic is the potential for an increased risk of thrombotic events. Patients were observed for a period of 72 hours for evidence of any thrombo-embolism. No patient in our study experienced a complication from the use of tranexamic acid, although no investigations beyond a physical examination and history taking were done.

Tranexamic acid 10mg/kg mixed in 100ml normal saline shortly after induction of anaesthesia over 15 min before skin incision,followed by infusion of 1mg/kg per hour upto closure of skin incision reduced both intraoperative and post operative bleeding in our patients who underwent total hip arthroplasty under general anaesthesia

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