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Revista Brasileira de Ortopedia

Print version ISSN 0102-3616On-line version ISSN 1982-4378

Rev. bras. ortop. vol.50 no.2 São Paulo Mar./Apr. 2015

http://dx.doi.org/10.1016/j.rboe.2015.03.007 

Original Article

Use of tranexamic acid for controlling bleeding in thoracolumbar scoliosis surgery with posterior instrumentation

Vinícius Magno da Rocha*  1 

Alderico Girão Campos de Barros1 

Cleiton Dias Naves1 

Nayara Lopes Gomes1 

Julie Calixto Lobo1 

Luís Cláudio Villela Schettino1 

Luís Eduardo Carelli Teixeira da Silva1 

1National Institute of Traumatology and Orthopedics, Rio de Janeiro, RJ, Brazil

ABSTRACT

OBJECTIVE:

Scoliosis surgery involves major blood loss and frequently requires blood transfusion. The cost and risks involved in using allogeneic blood have motivated investigation of methods capable of reducing patients' bleeding during operations. One of these methods is to use antifibrinolytic drugs, and tranexamic acid is among these. The aim of this study was to assess the use of this drug for controlling bleeding in surgery to treat idiopathic scoliosis.

METHODS:

This was a retrospective study in which the medical files of 40 patients who underwent thoracolumbar arthrodesis by means of a posterior route were analyzed. Of these cases, 21 used tranexamic acid and were placed in the test group. The others were placed in the control group. The mean volumes of bleeding during and after the operation and the need for blood transfusion were compared between the two groups.

RESULTS:

The group that used tranexamic acid had significantly less bleeding during the operation than the control group. There was no significant difference between the groups regarding postoperative bleeding and the need for blood transfusion.

CONCLUSIONS:

Tranexamic acid was effective in reducing bleeding during the operation, as demonstrated in other studies. The correlation between its use and the reduction in the need for blood transfusion is multifactorial and could not be established in this study. We believe that tranexamic acid may be a useful resource and that it deserves greater attention in randomized double-blind prospective series, with proper control over variables that directly influence blood loss.

Key words: Tranexamic acid; Scoliosis/surgery; Duration of bleeding; Blood transfusion

Introduction

Surgical correction of scoliosis involves significant blood loss of multifactorial origin. The duration of the surgical procedure, the severity and type of the deformity, the technique used, the mean perioperative arterial pressure and the hemostasis strategies are among the variables that directly influence the amount of bleeding.1 , 2 , 3 , 4 , 5 and 6

Within this scenario, the need for blood transfusions is a reality that is of concern for surgeons and attracts the attention of researchers. Use of allogeneic blood with the aim of maintaining tissue perfusion and preventing injuries to target organs in patients with large-volume blood losses is not risk-free. Transmission of viral diseases, immunological reactions and reductions in coagulation factors are known to be complications of blood transfusion.1 , 2 and 4

Given this situation, a variety of strategies have already been proposed in attempts to diminish the dependence on allogeneic blood in major surgery. These include storage of autologous blood before the operation, normovolemic hemodilution, hypotensive anesthesia, use of a cell recovery machine and use of drugs with antifibrinolytic properties, such as aprotinin, epsilon-aminocaproic acid and tranexamic acid.6 , 7 , 8 , 9 and 10

Tranexamic acid is a synthetic antifibrinolytic drug that has the resultant effect of forming a reversible complex with plasminogen and plasmin. It inhibits fibrinolysis, prevents lysis of fibrin coagulum and acts toward partial blocking of the platelet aggregation induced by plasmin.11 and 12 Because of its low cost and because its side effects are small, studies have been conducted in different parts of the world in attempts to evaluate its efficacy for controlling perioperative bleeding in major surgery.2 , 7 , 8 , 9 , 10 , 11 and 12

In our institution, tranexamic acid has recently been used in operations to treat idiopathic scoliosis. The surgeons counted on its efficacy for reducing the bleeding consequent to the surgical procedure, thus hoping to reduce the risk for patients and to lead to lower need for blood transfusions.

The objective of this study was to document the influence of tranexamic acid on the bleeding inherent to procedures for treating idiopathic scoliosis with posterior instrumentation, and to ascertain whether the expected reduction in bleeding was capable of reducing the need for blood transfusion.

Methods

Profile of the sample

This was a retrospective cohort study on 40 patients who underwent operations to correct idiopathic scoliosis between December 2012 and March 2013. The study was approved by the research ethics committee of the center where it was conducted (CAAE-15734413.6.0000.5273).

The medical files of patients who underwent arthrodesis via a posterior route with six or more levels of arthrodesis, whose bleeding consequent to the procedure was adequately documented, were analyzed. We used the selection criteria listed in Table 1.

Table 1  Sample selection criteria. 

Inclusion criteria
Age between 10 and 30 years
Body mass index between the 5th and 95th percentiles for the age
Idiopathic scoliosis
Posterior arthrodesis with fusion of six or more levels

Exclusion criteria
Mean perioperative arterial pressure exceeding 85 mmHg
Congenital or syndromic scoliosis
Previous spinal surgery
Use of the drug not in accordance with the standardized protocol

Data analyzed

Data that were considered relevant for the statistical analyses were gathered from the medical files. These included: (1) patient's age; (2) patient's weight at the time of the operation; (3) duration of the procedure from the time of the skin incision until its closure; (4) severity of the deformity; (5) bleeding documented in the medical file; and (6) use of blood transfusions.

The number of levels subjected to arthrodesis was used as a variable for estimating the severity of the deformities.

The perioperative bleeding estimated in this study was measured as the blood collected through the suction drains of the surgical site during the operation plus the blood absorbed in the surgical compressive dressings. For the calculations, the density of human blood was taken to be 1.053 g/mL and the quantity of saline solution used for irrigation of the surgical site was discounted.

The postoperative bleeding was also taken into consideration and was estimated from the output of the vacuum drains that were installed subcutaneously over the first 24 h after the operation.

Surgical technique

Three teams participated in the operations on the patients selected. Basically, the surgical technique involved a skin incision on the midline above the spinal processes, followed by dissection of the soft tissues until achieving exposure of the vertebrae. Careful hemostasis was undertaken. The ligaments and facets were released in order to gain spinal mobility, and pedicle screws and pins were used to enable correction and stabilization of the deformity. Autologous grafts coming from the spinal processes and iliac crest were used to enable vertebral fusion. Vacuum suction drains were positioned in the subcutaneous layer in order to allow adequate drainage of the surgical wound during the postoperative period.

Use of the drug

In our institution, we follow a protocol in which tranexamic acid is used at an attack dose of 100 mg/kg of body weight, administered over the 30-minute period prior to making the skin incision. A maximum dose of 2 g of the drug is observed. After the incision has been made, continual infusion is maintained at the rate of 30 mg/kg/h until the end of the procedure, i.e. when the skin has been closed. This protocol has already been used safely in other centers.2 and 13

Division of the groups

Among the 40 patients selected, 21 received tranexamic acid in accordance with the administration protocol (test group), while the other 19 were operated without receiving the drug (control group).

Evaluation of complications

The patients involved in the study remained in hospital for an average of five days after the operation. After this period, they started to undergo periodic outpatient follow-ups. A search was made in the medical files of the patients who received tranexamic acid with the aim of identifying any possible complications relating to use of the drug, especially those resulting from thromboembolic events, including venous thrombosis, pulmonary embolism, arterial occlusion, kidney failure, etc.

Statistical analysis

The results were expressed as means ± SD (standard deviation). For comparisons, Student's t test or the Mann-Whitney test was used, when appropriate. Correlations between the study variables were determined using the Spearman or Pearson correlation coefficient. The nominal variables were evaluated using the Chi-square test. Results were accepted as statistically significant with p < 0.05. The statistical analyses were performed using the Stata 11.2 software (StataCorp, Texas, USA).

Results

Comparison between the test group (tranexamic acid) and the control group

Overall, the groups studied were comparable and there was no significant difference between them regarding age, body weight, number of levels subjected to arthrodesis and duration of the operation (Table 2).

Table 2  Profiles of the groups studied. 

Control Tranexamic acid p-Value
Number of patients 19 21
Age (years) 21.6 ± 8.0 18.0 ± 4.4 0.1463
Weight (kg) 51.8 ± 5.9 55.5 ± 6.1 0.0628
Number of levels fused 9.2 ± 2.3 9.4 ± 2.2 0.7624
Duration of operation (h) 4.3 ± 1.4 4.0 ± 1.2 0.5291

Mean blood loss

The mean perioperative blood loss among the patients who received tranexamic acid was 747.6 ± 265.9 mL. In the control group, it was 996 ± 342.0 mL, with a statistically significant difference (p = 0.01) ( Table 3).

Table 3  Mean amount of bleeding in the groups studied. 

Control Tranexamic acid
Perioperative loss (mL) 996.0 ± 342.0 747.6 ± 265.9
Postoperative loss (mL) 410.5 ± 215.2 349.8 ± 268.4
Total loss (mL) 1406.5 ± 372.1 1097.3 ± 323.9

In relation to postoperative bleeding, we observed that the control group presented a mean bleeding level that was 60.7 mL greater than that of the patients who received tranexamic acid. This difference was not statistically significant.

Percentage perioperative blood volume loss

Since the blood volume of each individual is a variable link directly to body weight, the percentage perioperative blood volume loss of each patient was estimated by taking the mean volume of 70 mL per kg of body weight. In this manner, an index capable of correlating the volume of blood lost during the operation with the estimated total blood volume could be created.

It was observed that the percentage perioperative blood volume loss in the tranexamic acid group (mean of 19.4 ± 7%) was significantly lower than that of the control group (mean of 27.6 ± 9.4%) (p = 0.008) ( Fig. 1).

Fig. 1 -  Comparison between percentage blood volume losses in the control and test groups. 

We also observed that there was a positive linear correlation between the percentage perioperative blood volume loss and the duration of the operation, for both groups (r = 0.369; p = 0.0191).

Relationship between the percentage perioperative blood volume loss and the number of levels subjected to arthrodesis (loss/level)

Another important variable considered in analyzing the results was the number of levels subjected to arthrodesis. Patients with curves that are more severe generally require procedures that encompass larger numbers of vertebrae. This is directly reflected in the duration of the surgical procedure and the amount of perioperative bleeding. In view of this reality, we created an index correlating the percentage perioperative blood volume loss and the number of levels subjected to arthrodesis (loss/level).

We observed that the tranexamic acid group had a significantly lower loss/level ratio than that of the control group (p = 0.01) ( Table 4).

Table 4  Percentage perioperative blood volume loss. 

Control Tranexamic acid p-Value
Blood volume loss (%) 27.6 ± 9.4 19.4 ± 7.0 0.0083
Number of levels subjected to arthrodesis 9.2 ± 2.3 9.4 ± 2.2 0.7624
Loss/level 3.2 ± 1.3 2.1 ± 0.6 0.0101

Relationship between the percentage perioperative blood volume loss, the number of levels subjected to arthrodesis and the duration of the operation

Considering that the percentage perioperative blood volume loss has direct relationships with the number of levels subjected to arthrodesis and the duration of the operation, we applied linear regression in order to analyze the relationship between the use of tranexamic acid and the percentage perioperative blood volume loss, controlled for the number levels subjected to arthrodesis and the duration of the operation. We found that use of this drug reduced the percentage blood volume loss by 7.1% (p = 0.001).

Need for blood transfusion

In the control group, the mean blood volume transfused was 176.3 ± 252.6 mL per patient. In the test group, it was 111.1 ± 216.5 mL. Blood transfusion was required for 47.4% of the control group and 28.6% of the group that received the drug, i.e. the drug reduced the need for transfusion by 18.8%. The Chi-square test did not show any evidence capable of correlating the use of the drug with this reduction, for a 95% confidence level (p = 0.220).

Complications resulting from use of tranexamic acid

During the postoperative follow-up period, there were no clinical or surgical complications attributable to use of tranexamic acid.

Discussion

Our results showed that the group that used tranexamic acid had a lower mean level of perioperative bleeding. Other studies that have analyzed this relationship have obtained similar results.2 , 8 , 9 , 10 , 11 , 12 , 13 and 14

The percentage perioperative blood volume loss provides a closer representation of the systemic consequences resulting from blood loss than does direct analysis of the bleeding in absolute values. This is because by correlating bleeding, blood volume and body weight, data of greater reliability regarding the impact of blood loss on patients' homeostasis are furnished. Our results showed that the group that used tranexamic acid had lower percentage perioperative blood volume loss and reproduced the findings of another retrospective cohort study that used the same index.13

The postoperative loss was also lower in the group that used tranexamic acid, but this difference was non-significant. In our study, certain factors may explain these results. The plasma half-life of this drug is relatively short (3.1 h) and its effect cannot be guaranteed throughout the 24-h period subsequent to the surgical procedure. Moreover, the chances that the material discharged through the drain might have also included seroma and other tissue degradation products was not taken into consideration by the professionals who measured the contents of the collection flasks and, thus, measurement bias may have occurred. Only one study has demonstrated a significant difference in postoperative bleeding between groups that used this drug and groups that used placebo.10

The reduction in the need for transfusion observed in the group that used tranexamic acid was not significant for the number of patients involved. Although studies with different designs have obtained similar results,2 , 8 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 and 23 we take the view that the model of our study was not the most appropriate one for analyzing this outcome. Furthermore, we noted that there was no standardization of the parameters used by surgical and anesthesia teams with regard to using homologous or autologous blood. Use of mean arterial pressure greater than 85 mmHg as an exclusion criterion may not have been sufficient to neutralize the influence of higher blood pressure levels on perioperative bleeding. We believe that keeping mean arterial pressure within a band would be more appropriate for controlling the impact of this variable on blood loss, as has been shown in some published series.3 , 4 , 5 , 24 , 25 and 26 The technical skill of each surgeon with regard to controlling hemostasis and the pedicular instrumentation is another important variable that should be taken into consideration. This may have interfered with the results between the groups, given that three different teams operated on the patients studied.3 and 26

Since the risk of complications inherent to using homologous blood is directly proportional to the quantity of blood used,27 and 28 the decrease in blood loss in the group that used tranexamic acid should be valued. Moreover, the reduction in perioperative blood loss may also diminish the risk of death, but this is a theoretical proposition that has not been assessed in any study.

The groups studied were statistically similar regarding age group, body weight, during of the operation and severity of the deformity, which diminished the interference of these variables in the study.3 , 4 and 5

The meta-analyses available still do not bring together numbers capable of guaranteeing the safety of tranexamic acid, for use in accordance with the protocol presented.25 and 27 In the present study, no complications were attributed to use of tranexamic acid. The number of complications reported in the literature so far has been very small and comparable with those seen in using placebo,26 , 27 , 28 and 29 bit the seriousness of the possible thromboembolic events makes it essential to implement regular follow-up for these patients.

The protocol for using tranexamic acid that was analyzed in the present study has already been applied by other authors. Its efficacy has been compared with placebo and with other antifibrinolytic drugs, and the results relating to its efficacy and safety have been promising.2 , 8 , 14 , 25 and 27 Studies using tranexamic acid at lower doses have not achieved the same proportional reduction in perioperative bleeding.20 and 23

Conclusion

Use of tranexamic acid is a low-cost, effective and safe option for reducing perioperative bleeding during operations to treat scoliosis with posterior instrumentation. Its efficacy in reducing the need for blood transfusion is a multifactorial phenomenon that could not be demonstrated in the present study.

Randomized prospective clinical studies with proper blinding of the surgical and anesthesia teams thus become necessary in order to evaluate the impact of tranexamic acid on the need for blood transfusion and contribute toward rationalizing protocols so as to make them more effective and safer in using this drug.

References

1. Brecher ME, Monk T, Goodnough LT. A standardized method for calculating blood loss. Transfusion. 1997;37(10):1070-4. [ Links ]

2. Dhawale AA, Shah SA, Sponseller PD, Bastrom T, Neiss G, Yorgova P, et al. Are antifibrinolytics helpful in decreasing blood loss and transfusions during spinal fusion surgery in children with cerebral palsy scoliosis? Spine [Phila, PA, 1976]. 2012;37(9):549-55. [ Links ]

3. Guay J, Haig M, Lortie L, Guertin MC, Poitras B. Predicting blood loss in surgery for idiopathic scoliosis. Can J Anaesth. 1994;41(9):775-81. [ Links ]

4. Hu SS. Blood loss in adult spinal surgery. Eur Spine J. 2004;13(1):3-5. [ Links ]

5. Hur SR, Huizenga BA, Major M. Acute normovolemic hemodilution combined with hypotensive anesthesia and other techniques to avoid homologous transfusion in spinal fusion surgery. Spine [Phila, PA, 1976]. 1992;17(8):867-73. [ Links ]

6. Imbesi S, Nettis E, Minciullo PL, Leo ED, Saija A, Vacca A, et al. Hypersensitivity to tranexamic acid: a wide spectrum of adverse reactions. Pharm World Sci. 2010;32(4):416-9. [ Links ]

7. Neilipovitz DT. Tranexamic acid for major spinal surgery. Eur Spine J. 2004;13(1):62-5. [ Links ]

8. Yagi M, Machida M, Hasegawa A, Nagoshi N, Lizuka S, Kaneko S, et al. Does the intra-operative tranexamic acid decrease operative blood loss during posterior spinal fusion for treatment of adolescent idiopathic scoliosis? Spine [Phila, PA, 1976]. 2012;37(21):1336-42. [ Links ]

9. Lenke LG, O'Leary PT, Bridwell KH, Sides BA, Koester LA, Blanke KM. Posterior vertebral column resection for severe pediatric deformity. Spine [Phila, PA, 1976]. 2009;34(20):2213-21. [ Links ]

10. Neilipovitz DT, Murto K, Hall L, Barrowman NJ, Splinter WM. A randomized trial of tranexamic acid to reduce blood transfusion for scoliosis surgery. Anesth Analg. 2001;93(1):82-7. [ Links ]

11. Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology. 2005;102(4):727-32. [ Links ]

12. Casati V, Guzzon D, Oppizzi M, Cossolini M, Torri G, Calori G, et al. Hemostatic effects of aprotinin, tranexamic acid and epsilon-aminocaproic acid in primary cardiac surgery. Ann Thorac Surg. 1999;68(6):2252-7. [ Links ]

13. Shapiro F, Zurakowski D, Sethna NF. Tranexamic acid diminishes intraoperative blood loss and transfusion in spinal fusions for Duchenne muscular dystrophy scoliosis. Spine [Phila, PA, 1976]. 2007;32(20):2278-83. [ Links ]

14. Pinosky ML, Kennedy DJ, Fishman RL, Reeves ST, Alpert CC, Ecklund J, et al. Tranexamic acid reduces bleeding after cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. J Card Surg. 1997;12(5):330-8. [ Links ]

15. Henry DA, Moxey AJ, Carless PA, O'Connell D, McClelland B, Henderson KM, et al. Anti-fibrinolytic use for minimizing perioperative allogeneic blood transfusion. CDS Rev. 2007;(4):CD001886. [ Links ]

16. Howe C, Paschall C, Panwalkar A, Beal J, Potti A. Predicting blood loss in surgery for idiopathic scoliosis. Can J Anaesth. 1994;41(9):775-81. [ Links ]

17. Baldus CR, Bridwell KH, Lenke LG, Okubadejo GO. Can we safely reduce blood loss during lumbar pedicle subtraction osteotomy procedures using tranexamic acid or aprotinin? A comparative study with controls. Spine [Phila, PA, 1976]. 2010;35(2):235-9. [ Links ]

18. Farrokhi MR, Kazemi AP, Eftekharian HR, Akbari K. Efficacy of prophylactic low dose of tranexamic acid in spinal fixation surgery: a randomized clinical trial. J Neurosurg Anesthesiol. 2011;23(4):290-6. [ Links ]

19. Grant JA, Howard J, Luntley J, Harder J, Aleissa S, Parsons D. Perioperative blood transfusion requirements in pediatric scoliosis surgery - the efficacy of tranexamic acid. J Pediatr Orthop. 2009;29(3):300-4. [ Links ]

20. Caglar GS, Tasci Y, Kayikcioglu F, Haberal A. Intravenous tranexamic acid use in myomecomy: a prospective randomized double-blind placebo controlled study. Eur J Obstet Gynecol Reprod Biol. 2008;137(2):227-31. [ Links ]

21. Urban MK, Beckman J, Gordon M, Urquhart B, Boachie-Adjei O. The efficacy of antifibrinolytics in the reduction of blood loss during complex adult reconstructive spine surgery. Spine [Phila, PA, 1976]. 2001;26(10):1152-6. [ Links ]

22. Zufferey P, Merquiol F, Laporte S, Decousus H, Mismetti P, Auboyer C, et al. Do antifibrinolytics reduce allogeneic blood transfusion in orthopedic surgery? Anesthesiology. 2006;105(5):1034-46. [ Links ]

23. Verma K, Lonner B, Dean L, Vecchione D, Lafage V. Reduction of mean arterial pressure at incision reduces operative blood loss in adolescent idiopathic scoliosis. Spine Deformity. 2013;1(2):115-22. [ Links ]

24. Tzortzopoulou A, Cepeda MS, Schumann R, Carr DB. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. CDS Rev. 2008;(3):CD006883. [ Links ]

25. Nuttall GA, Horlocker TT, Santrach PJ, Oliver WC, Dekutoski MB, Bryant S. Predictors of blood transfusions in spinal instrumentation and fusion surgery. Spine [Phila, PA, 1976]. 2000;25(5):596-601. [ Links ]

26. Gill JB, Chin Y, Levin A, Fang D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008;90(11):2399-407. [ Links ]

27. Meunier A, Petersson A, Good L, Berlin G. Validation of a haemoglobin dilution method for estimation of blood loss. Vox Sang. 2008;95(2):120-4. [ Links ]

28. Karkouti K, Dattilo KM. Perioperative hemostasis and thrombosis. Can J Anaesth. 2006;53(12): 1260-2. [ Links ]

29. Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine [Phila, PA, 1976]. 2008;33(24):2577-80. [ Links ]

Work developed at the National Institute of Traumatology and Orthopedics (INTO), Rio de Janeiro, RJ, Brazil.

Received: July 31, 2013; Accepted: May 19, 2014

* Corresponding author. E-mails: viniciusmagnodarocha@gmail.com, vinimedrj@yahoo.com.br (V.M. da Rocha).

Conflicts of interest The authors declare no conflicts of interest.

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