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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 6
| Issue : 2 | Page : 137-141 |
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Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for lumbar canal stenosis with/without instability: A prospective randomized double-blinded placebo control study
S Srinivasalu, Milen E Arouje, B Mallikarjunaswamy, M Madan Mohan, NV Ankith, Mahesh Shekoba
Department of Orthopedics, St. John's Medical College and Hospital, Bengaluru, Karnataka, India
| Date of Submission | 01-Aug-2022 |
| Date of Decision | 25-Oct-2022 |
| Date of Acceptance | 17-Feb-2023 |
| Date of Web Publication | 3-May-2023 |
Correspondence Address:
M Madan Mohan
St. John's Medical College Hospital, Sarjapur Road, Bengaluru - 560 034, Karnataka
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jodp.jodp_60_22
Introduction: Lumbar stenosis is a common disorder, commonly occurring at L4-5, with up to 91% of patients having neural compression at this level. Degenerative spinal stenosis with or without instability requiring multilevel spine surgery is associated with large blood loss. Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. The objectives of the study were to assess the efficacy of TXA in reducing perioperative blood loss and assess the complications associated with its administration and need for blood transfusion during posterior lumbar spine surgery for lumbar canal stenosis (LCS). Methodology: Between November 2018 and August 2020, 130 adult patients (age 18–70 years) with LCS undergoing posterior lumbar instrumented spinal fusions at our institution were divided into TXA and control groups. Outcomes assessed are intraoperative blood loss (IOBL) and postoperative blood loss (POBL), hematocrit, need for allogeneic blood transfusion, and complications such as deep vein thrombosis, myocardial infarction, stroke, and seizures postoperatively. Results: There was a statistically highly significant reduction in the mean IOBL, POBL, mean postoperative hemoglobin, and postoperative packed cell volume in the tranexamic group compared to the control group. There was no significant statistical difference in need for blood transfusion among the two groups. No complications were observed in either group associated with administration of TXA. Conclusion: Prophylactic use of low-dose TXA provides an effective and safe method for reduction of blood loss during and after LCS surgeries. Low-dose TXA does not significantly affect the duration of surgery or need for blood transfusion. Higher-level multicentric studies are required to evaluate the safety of TXA in multilevel lumbar spine surgeries.
Keywords: Intraoperative blood loss, postoperative blood loss, tranexamic acid
How to cite this article:
Srinivasalu S, Arouje ME, Mallikarjunaswamy B, Mohan M M, Ankith N V, Shekoba M. Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for lumbar canal stenosis with/without instability: A prospective randomized double-blinded placebo control study. J Orthop Dis Traumatol 2023;6:137-41 |
How to cite this URL:
Srinivasalu S, Arouje ME, Mallikarjunaswamy B, Mohan M M, Ankith N V, Shekoba M. Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for lumbar canal stenosis with/without instability: A prospective randomized double-blinded placebo control study. J Orthop Dis Traumatol [serial online] 2023 [cited 2023 Jun 4];6:137-41. Available from: https://jodt.org/text.asp?2023/6/2/137/375552 |
| Introduction | |  |
Lumbar canal stenosis (LCS) is one of the most common spine diseases, and most of these patients undergo posterior decompression alone, or decompression and fusion, with or without instrumentation.[1] Degenerative spinal stenosis with or without instability requiring multilevel spine surgery is associated with major blood loss.[2] Surgical blood loss averages over 800 ml (range 100–3100 ml) for noninstrumented fusions to 1517 ml (range 360–7000 ml) for instrumented fusions for lumbar fusion surgery.[3]
Typical consequences of blood loss are severe hypotension, metabolic acidosis, infections, acute lung injury and cerebral edema due to fluid shifts, cardiac arrest, and also extended operation times.[3] Some patients might also require an allogeneic blood transfusion, with its own risk of transfusion-acquired infectious diseases and immune suppression.[4]
Decreasing bleeding is not only important for keeping the patient's hemodynamic equilibrium but also for allowing a better visualization of the operative field, especially in spine surgery because of the vicinity of major and highly fragile neurologic structures.
Multiple methods have been introduced to reduce the perioperative blood loss and need of transfusions, such as preoperative autologous blood donation, hypotensive anesthesia, normovolemic hemodilution, and perioperative blood salvage.[5]
Antifibrinolytic use has aided in reducing blood loss in cardiac surgeries. Tranexamic acid (TXA), a synthetic lysine-analog antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery.[6]
This study was done to evaluate the efficacy of TXA in reducing blood loss in lumbar spine surgery with or without instability and also to assess whether TXA reduces need for blood transfusion and complications associated with TXA administration.
| Methodology | | |
All symptomatic patients with diagnosed LCS and confirmed with magnetic resonance imaging (MRI) with or without instability, for whom posterior decompression and instrumented fusion (single to three-level, posterolateral) was planned, were considered to take part in the study. Patients with known allergy to TXA, abnormal coagulation profile, significant cardiac/respiratory/renal or hepatic dysfunction, past history of thromboembolic events, and uncontrolled hypertension were excluded from this study. One hundred and thirty patients were included in this study.
Informed consent was taken. History, clinical evaluation, radiological evaluation with X-ray and MRI, and relevant baseline investigations were done and documented.
They were equally randomized into two groups using draw of lots.
- Group 1 – Patients undergoing posterior decompression and spine fixation with prior TXA injection (10 mg/kg intravenous [IV] 10 min before the surgery)
- Group 2 – Patients undergoing posterior decompression and spine fixation, without prior TXA injection (0.9% NS infusion).
The surgeon, anesthetist, and observer were blinded as to which solution was being given.
All patients were operated on in prone position, with the abdomen kept free of any pressure under hypotensive anesthesia. All the patients underwent posterior decompression by laminectomy with or without discectomy as indicated. All patients underwent fusion with pedicular screws and rod instrumentation. Cell-saver equipment was not used in this study.
Intraoperative blood loss (IOBL), during surgery in milliliters, was estimated using visual assessment of blood-soaked mops, gauzes from surgery, and collection in suction bottle (after subtracting amount of saline used for wash). Postoperative blood loss (POBL) was documented from the drain at 24 h and 48 h. The total blood loss (TBL) is a combination of IOBL and POBL. Postoperatively, hemoglobin (Hb), packed cell volume (PCV), and renal function tests were monitored.
The primary outcome was blood loss after the surgery, the secondary outcome was the number of packed cell transfusions, and the tertiary outcome was the complications of TXA such as allergy to TXA, deep-vein thrombosis (DVT), myocardial infarction, and cerebral vascular accident.
Statistical software
IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY, USA: IBM Corp and R Core Team (2021); R: A language and environment for statistical computing; and R Foundation for statistical computing, Vienna, Austria. URL https://www.R-project.org/have been used for the analysis of the data.
| Results | | |
A total of 130 patients were enrolled in the study, 65 in each group. Both the groups were well matched with regard to age, gender, body weight, and blood parameters with no statistical significance.
The descriptive statistics for the whole study population and group-wise statistics are reproduced in [Table 1], [Table 2], [Table 3]. The analytical statistics is reproduced in [Table 4].
The mean IOBL in Group 1 was 322.08 ± 98.79 and in Group 2 575.08 ± 120.5, respectively, and was statistically highly significant with P = 0.00001. The mean POBL in Group 1 was 174.62 ± 60.22 and in Group 2 229.92 ± 41.79, respectively, and was statistically highly significant with P = 0.00001.
The mean postoperative Hb in Group 1 and Group 2 was 12.03 ± 1.87 and 11.12 ± 1.43, respectively, and was statistically highly significant with P = 0.0021.
The mean postoperative PCV in Group 1 and Group 2 was 35.84 ± 4.85 and 33 ± 3.59, respectively, and was statistically significant with P = 0.0002. No statistical difference in number of packed red blood cell (PRBC) transfusion existed among the two groups, P = 0.253. No complications were observed in either group associated with administration of TXA.
The study did not show any statistical difference in the mean duration of surgery (128.25 ± 30.1 minutes in Group 1, and 136 ± 30.41 minutes).
| Discussion | | |
Lumbar spinal fusion surgery is one of the most commonly performed procedures in spine surgery. There are multitude factors that either enhance the risk of bleeding or require additional operative time in spine surgery, such as structural anatomy of the spine, spongy vertebrae with its good blood supply, and the delicate venous plexus wall that cannot constrict after injury.[7],[8] Due to the significant risks and complications associated with blood loss and allogeneic blood transfusions, there is a need to find safe and reliable ways to reduce blood loss during spinal surgery.[9],[10]
The use of pharmacological therapies to reduce blood loss and blood transfusions in surgery has historically been restricted to a few options: aprotinin, TXA and aminocaproic acid, desmopressin, and recombinant VIIa.[11],[12] Antifibrinolytic agents (aprotinin, TXA, and aminocaproic acid) have the best evidence supporting their use, especially in cardiac surgery, liver transplantation, and certain orthopedic surgical procedures. Multiple randomized trials have demonstrated their efficacy, not being negatively offset by serious adverse effects. In most situations, the lysine analogs are probably as effective as aprotinin and are economical; the evidence is stronger for TXA than for aminocaproic acid.[13]
Among patients undergoing major orthopedic and spine surgery, antifibrinolytic agents in comparison to placebo, help reduce bleeding, reduce the requirement of blood transfusion, without increasing significantly the risk of myocardial infarction, stroke, DVT, or pulmonary embolism.[14] It is widely accepted that TXA administration effectively reduces blood losses and transfusions in total knee arthroplasty (117–120). In contrast to the extensive evidence supporting the use of TXA for knee surgeries, there is a paucity of evidence for its role in spine surgeries. Currently, TXA administration in spinal surgery is largely surgeon dependent rather than a standard of care.[15]
In the present study, 130 patients of age 18–70 years who were diagnosed with LCS and posted for elective lumbar spine decompression and fusion were randomly assigned to the TXA group and placebo group. Both the groups were comparable in mean age, body weight, gender distribution, preoperative Hb, hematocrit values, and coagulation profile. Contributing factors that could alter blood loss were monitored during the study (mean arterial pressure, coagulation profile, and standardized anesthesia technique).
In our study, the mean intraoperative, postoperative as well as TBL was less in the TXA group as compared to the placebo group (P < 0.0001). There were also significant differences in postoperative Hb and PCV in the TXA group as compared with the placebo group (P < 0.0001). However, it is worth mentioning here that the blood transfusions received in both the groups were not statistically significant (P = 0.253). This result was consistent with the study by Carabini et al.[16] and Shapiro et al.[17] This discrepancy being most likely due to the small sample size. Yang et al. also in a meta-analysis of 9 studies comprising 581 patients, demonstrated that patients receiving TXA perioperatively, had a reduction of blood loss along with a statistically significant decrease in the need for blood transfusion.[18] Whereas Bai et al.,[19] in a meta-analysis of nine studies enrolling 713 patients, demonstrated that TXA could decrease the postoperative Hb loss, TBL, IBL, PBL, and without increasing the risk of the thrombotic event in posterior lumbar fusion surgery. However, there was no statistical difference in transfusion rate between the two groups.
It is important to establish the lower limit of effective dosing for TXA, given the association between high TXA doses and adverse neurologic effects unrelated to thromboembolic disease. Dose regimens of TXA vary widely in the literature, loading dose range from 2.5 mg/kg of BW to 100 mg/kg of BW and maintenance dose range from 0.25 mg/kg of BW to 4 mg/kg of BW/hour delivered for 1–12 h.[11]
In our study, only loading dose of 10 mg/kg of TXA was used. With this dose, adequate hemostasis was achieved (38% reduction in TBL). Elwatidy et al.,[20] who randomized 64 patients undergoing multilevel spine surgeries to a large dose of TXA (2 g in 100 ml in adults and 30 mg/kg of BW in children), and a maintenance dose (1 g in 100 ml infusion at a rate of 100 mg/h for adults, or 1 mg/kg of BW/h in children), reported a reduction of blood loss by 48% intraoperatively and 55% postoperatively in terms of drain output in the TXA group compared to the placebo group. Wong et al.[21] administered TXA intravenously with an initial bolus dosage of 10 mg/kg and 1 mg/kg/h of maintenance infusion until skin closure, for 147 patients, who underwent elective posterior instrumented spinal fusion. They demonstrated a reduction as much as 30% of estimated blood loss from the procedure, in patients who were given IV administration of TXA.
Raksakietisak et al. showed a statistically significant decreased blood loss and decreased the use of PRBCs in patients receiving TXA (two doses of TXA at 15 mg/kg) compared to those who received placebo following a complex laminectomy procedure.[22]
Sethna et al. randomized 44 pediatric patients undergoing scoliosis surgery to either recieve a large dose of TXA (100 mg/kg of body weight as bolus dose given before surgery followed by infusion of 10 mg/kg BW/h during surgery) or 0.9% saline (placebo group). In the TXA group blood loss was reduced by 41% compared to the placebo group.[4]
Large dose was reported with serious side effects such as disturbed color vision, numbness or weakness, confusion, or allergic reactions. In our study, we did not find any complications associated with administration of TXA such as suspected medication or allergic reaction, myocardial infarction, seizures, headaches, stroke, renal failure, visual disturbances such as impaired color vision, DVT, or pulmonary embolism, which was consistent with the results of previous studies.[4],[14],[17],[23]
Correlation analysis showed duration of surgery, TXA, and level of surgery as primary predictors of blood loss in lumbar spine surgery. However, linear regression analysis showed that after controlling for level, IOBL was 252 ml more in the placebo group when compared to the TXA group and was statistically significant (P < 0.00001). Postoperative blood loss after adjusting for level was 55 ml more in the placebo group when compared with the TXA group and was statistically significant (P < 0.00001).
From our study, low-dose TXA helps in reducing intraoperative and POBL; however, it did not significantly reduce need for blood transfusion between the groups and there was no significant difference found between the duration of surgeries. No complications were observed with administration of TXA.
| Summary | | |
One hundred and thirty consenting patients scheduled for elective lumbar spine decompression and fusion surgery by posterior laminectomy with pedicular screw and rod instrumentation for LCS were entered into the study and were equally randomized to receive either TXA or placebo. The blood loss in both the groups was compared with the following observations:
All patients in the TXA group had significantly reduced TBL, IOBL, and POBL when compared with the placebo group.
There was no statistically significant difference in duration of surgeries between the control and treatment groups.
Although no statistically significant difference between the two groups on account of requiring blood transfusion, a marked difference was seen clinically between the two groups: the number of PRBC received in Groups 1 and 2 was 15 and 24, respectively.
Further, no complications were observed with the use of TXA such as allergic reactions, seizures, myocardial infarction, stroke, and DVT.
| Conclusion | | |
Prophylactic use of low-dose TXA provides an effective and safe method for reduction of blood loss during and after LCS surgeries.
Low-dose TXA does not significantly affect the duration of surgery or need for blood transfusion.
Higher-level multicentric studies are required to evaluate the safety of TXA in multilevel lumbar spine surgeries.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]
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