|Ahead of print publication
A study to evaluate reduction in blood loss by topical application of tranexamic acid in burn wound surgery
Amitabh Mohan1, G Vishwanath2, Nagamahendran Rajendran1
1 Department of Reconstructive Surgery, INHS Asvini, Colaba, Mumbai, Maharashtra, India
2 Consultant Reconstructive Surgery & Ex Additional Director General Medical Services (Navy), IHQ MoD (Navy), New Delhi, India
|Date of Submission||28-Mar-2020|
|Date of Decision||05-Aug-2020|
|Date of Acceptance||07-Aug-2020|
|Date of Web Publication||09-Dec-2020|
Resident, Department of General Surgery, INHS Asvini, Colaba, Mumbai, Maharashtra – 400005
Source of Support: None, Conflict of Interest: None
Background: Blood loss and problems associated with blood transfusion in burn wound excision is a major challenge a surgeon has to face. Topical application of antifibrinolytics has been used in many surgical fields. This study was conducted to assess the reduction of blood loss in burn wound excision by topical application of tranexamic acid. Materials and Methods: This Prospective observational study was conducted in a tertiary care hospital between February 2018 and May 2019. Results: In this study, we observe that by adding 0.5% tranexamic acid to 1 in 200,000 adrenalin topical solution, blood loss can be reduced while burns excision and skin grafting. In this study, after the application of tranexamic acid, the average blood loss per unit area reduced by 36% with significant P < 0.05. Conclusions: The use of tranexamic acid is effective and safe to use for topical use in concentration of 0.5% for reduction of blood loss in burn wound excision. However, further study with larger study group, should be done to confirm the findings of this study and further authenticating the results.
Keywords: Burn wound injury, excision in burns, tranexamic acid
| Introduction|| |
Blood loss associated with burn wound excision is a challenging problem. Several methods have been described for achieving hemostasis during burn wound surgery which includes physical measure such as elevation of part, electro cautery, and tourniquet application and pharmacological measures such as topical adrenaline, topical tranexamic acid, topical thrombin, fibrin sealant, subeschar adrenalin infiltration, systemic therapy with intravenous tranexamic acid, and recombinant factor VIIa which is not routinely recommended. The indirect benefit of these measures is potential reduction of rate of blood transfusion-related infection as well as prevention of serious allergic reaction.
Early excision and grafting is associated with risk of significant blood loss. One of the most successful pharmacologic strategies for reducing blood loss involve prophylactic intravenous administration of drugs that inhibit fibrinolysis, such aprotinin and tranexamic acid. However, their use has not yet been universally accepted due to their cost, as well as to the concern that they may induce a state of hypercoagulability after surgery. Tranexamic acid has been shown to reduce blood loss in patients with both normal and exaggerated fibrinolytic responses to surgery, without apparently increasing the risk of postoperative complications.
In the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage trial involving 20, 211 adult patients with trauma, tranexamic acid was shown to significantly reduce all-cause mortality and death due to bleeding, without any increase in vaso-occlusive events. The present study was done to evaluate the reduction in blood loss by topical application of tranexamic acid during burn wound surgery.
| Materials and Methods|| |
This comparative observational study was conducted at the department of plastic surgery in a tertiary care hospital between February 2018 and May 2019. The primary objective was to evaluate the difference in blood loss during burn wound surgery when hemostasis is achieved with topical application of adrenalin or adrenalin and tranexamic acid together. The secondary objective was to assess the difference in success in graft take in both the groups of the studies.
Patients of the burn injury with corresponding area of burns on the body were selected for the study. Patients were included in the study only after getting informed voluntary written consent. A total of 45 patients were enrolled in this study [Flow Chart 1]. Seven patients refused to participate and hence excluded. A total of 38 patients were finally included as study population.
Corresponding area of burn on each patient formed control group and study group, however, the selection of site for the application of adrenalin or adrenalin and tranexamic acid over the study group and control group was selected by random number table. All patients were evaluated with preoperative hemogram, coagulogram, platelet count, serum electrolytes, and kidney function test. All patients were hydrated with 1000 ml of normal saline. After adequate resuscitation and hemodynamic stability, they were taken up for excision of burn wound and skin grafting of the corresponding areas [Figure 1] and [Figure 2]. The two corresponding areas were randomly allocated to either Group A (control group) or Group B (study group).
|Figure 1: Primary excision bilateral lower limb ready for grafting posthemostatic application|
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|Figure 2: Burn wound bilateral thigh post excision ready for skin grafting|
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In Group A, only topical Adrenalin solution (1:200,000) was applied on the burn wound area selected for excision and grafting, after excising the wound, with soaked sponge for 5–10 min and in Group B, a solution of adrenalin and tranexamic acid (1:200,000 adrenalin and 1000 mg of tranexamic acid in 200 ml normal saline) was applied, after excising the wound, for 5–10 min to achieve hemostasis. In both the groups, the solution used was freshly prepared just before the surgery. In both the groups, hemostasis was assessed after 5 min of topical application of hemostatic solution and if still there is bleeding fresh sponge soaked in the hemostatic solution was used for another 5 min. Sterile polydrape was used and care was taken during surgery so that no spillage of hemostatic solution or blood occurs from the area being treated. Blood soaked sponge was weighed and counted separately for Groups A and B respectively and documented.
Weight of soaked sponges with hemostatic solution (both adrenalin and adrenalin and tranexamic acid together), of size 10 × 6 inches, was documented separately. Average weight of one soaked sponge piece was calculated. The average weight of one hemostatic solution soaked sponge was used for calculating blood loss [Figure 3] and [Figure 4]. Every milligram change in the weight of the sponge which is soaked in hemostatic solution is equal to same amount of blood loss in milliliter.
Imprint of the corresponding burn wound planned for surgery was taken preoperatively over a paper and the area was calculated as per the chart available commercially [Figure 5]. The amount of blood loss per square centimeter is calculated by dividing total blood loss from treated burn wound by area of the treated burn wound, the value of the same was expressed in ml/cm2.
Two groups were compared in terms of blood loss per unit area treated, success of skin graft taken and complications. Each patient’s demographic profile including age, sex, timing of surgery in relation to time of burns, total burn surface area (TBSA), corresponding area of burns (both upper limb, both lower limb, and area on each side of mid line over the trunk), blood loss in ml/cm2, complications, and graft take were compared.
| Results|| |
In 38 cases, there were total of 61 corresponding areas in different anatomical regions of the body. As in this study, the same individual is acting as control and test, demographic profile is same in both the groups and selection bias was reduced. The data were subjected to appropriate statistical analysis.
The youngest patient in this series was 15 years of age and oldest patient was of 47 years of age. In this study, 60% of the patients were between 20 and 40 years of age as this is the working group of people who are exposed to the maximum risk of burns. There were 25 males and 13 females [Table 1]. Females were 34% and males comprised 66% of cases. TBSA of burn ranged from 15% to 50%. Patients more than 50% TBSA were not included in this study. About 58% of patients had TBSA of 21%–40%. Average TBSA in this study was 31%. Patients with corresponding areas in the anatomical region of both upper limbs, both lower limbs and trunk, such as chest wall and abdominal wall were selected for this study. There were 25 areas (41%) of upper limbs, 16 areas (26%) of lower limbs and 20 areas (33%) were of abdominal and chest wall area. Areas symmetrical in distribution were selected and nonsymmetrical areas were not included in this study. Forty-one percent of patients were of upper limb involvement.
In this study, the size of the burn wound area ranged from 98 cm2 to 547 cm2. The overall average size of burn wound area treated was 218.4 cm2 in Group A and 224.5 cm2 in Group B which was comparable (P = 0.644) [Table 2]. Average size of the burn wound is comparable and as shown in the table with insignificant P value. The Average size of burn wound area treated in upper limb in Group A was 248 cm2 and in Group B was 249.7 cm2 (P = 0.94). The average size of burn wound area treated in trunk was also comparable, in Group A, it was 189 cm2 and in Group B was 192 cm2 (P = 0.83). The average size of area of burn wound area treated in lower limb in Group A was 208.8 cm2 and in Group B was 225 (P = 0.55). The overall average amount of blood loss was 444.3 ml in Group A and 292.7 ml in Group B, on statistical analysis with unpaired t-test P value was found to be of 0.001 which was significant. The average amount reduction in blood loss In Group B as compared to Group A was 36%.
Average amount of blood loss in different anatomical region shows that blood loss in upper limb in Group A was 509.2 ml and in Group B was 332.6 ml (P ≤ 0.0001) which was significant. The average amount of blood loss in trunk in Group A was 387.6 ml and in Group B was 250.9 ml (P ≤ 0.0001) which is significant. The average amount of blood loss in lower limb was also significant, in Group A it was 413.6 ml and in Group B was 282.6 ml (P = 0.0047). This shows that reduction in blood loss in Group B was significant.
Blood loss in each group was calculated as per the formula discussed. It has clearly shown that blood loss was significantly low in Group B that is test group as compared to control that is Group A. On statistical analysis with unpaired t-test, it was found the P = 0.001, which is significant. On follow-up, none of the patients found to have any local or systemic complication related to the use of tranexamic acid.
Healed Split Thickness Graft take in both the groups were comparable. Average healed burn wound area managed with split thickness skin graft in this study in Group A was 199.8 cm2 and in Group B was 206.2 cm2 at 3 weeks (P = 0.586). Average healed skin graft at 3 weeks was 92% in both the groups. None of the cases had graft loss.
| Discussion|| |
Perioperative bleeding is a potential complication of major surgical procedures like excision and skin grafting in burn wound that increases morbidity and mortality. Actively bleeding patients commonly undergo surgical re-exploration; receive transfusion of red blood cells or other blood products. Topical fibrinolytics have historically been used for traumatic hyphema, gynecological, orthopedics, endoscopic sinus surgeries, cardiac surgeries, and dental procedures. In an effort to apply this technique to the perioperative setting, several studies have investigated the use of topical antifibrinolytics for reduction of intraoperative bleeding and they have shown significant reduction in blood loss.,,, Till now, very few studies are reported in which antifibrinolytics were used in burn surgeries.
In this study, we have selected thermal burn patients ranging in age from 15 to 47 years and 60% of the patients were between 20 and 40 years of age as this refers to working group of people who are exposed to the maximum risk of burns. This finding is in corroboration of study by Jagannath et al., in which majority of cases (55.8%) were in the age group of 21–40 years male to female ratio in other studies were found to be 0.57–1.0 and 2–7, females were more affected in burn injuries in India as they are more exposed to fire while cooking and accidental burn was the major cause. In a study done by Ravikumar G et al. the TBSA was ranging from 10% to 100% with mean TBSA of 11.4 ± 2.95 and in another study conducted by Gandhari basu et al. the average TBSA affected was 41.3% In this study, the TBSA was ranging from 15% to 50% with average TBSA of 31%.
Average amount of blood loss in both the groups was recorded and compared. The overall average amount of blood loss in Group A was 444.3 ml with standard error of 19.3 ml and average amount of blood loss in Group B was 292.7 ml with standard error of 13.1 with significant P < 0.0001. This shows that there is significant amount of reduction of blood loss by topical application of 0.5% tranexamic acid during burn wound excision. In terms of percentage the reduction in blood loss amounts to 36% reduction which is significant. Other studies carried out in cardiac surgeries, gynecologic, and endoscopic sinus surgery amount to similar amount of reduction in blood loss using tranexamic acid.,, Nuhi et al. have found that tranexamic acid significantly decreased hemorrhage without increasing side effects such as alteration in coagulation parameters, hemodynamic changes, and vomiting and nausea. The use of tranexamic acid can avoid the need for antihypertensive agents to reduce blood loss in endoscopic sinus surgery (ESS).
In this study, average calculated amount of blood loss per unit area is 2.03 ml/cm2 in Group A and 1.30 ml/cm2 in Group B. This has shown reduction in blood loss of 0.73 ml/cm2 which amounts to 36% of reduction. This is in concordance to other studies which has shown similar amount of reduction of blood loss., Several controlled clinical trials have shown that tranexamic acid taken during menstruation reduced blood loss by 34%–59% compared with placebo or controls., A meta-analysis of total knee arthroplasty showed that comparing with only intravenous tranexamic acid, combined use of intravenous and topical tranexamic acid can significantly reduce blood loss and transfusion rate in primary total joint arthroplasty without increasing the risk of thrombotic complications.
The likely explanation for the reduction of blood loss is, tranexamic acid inhibits plasminogen/plasmin-mediated fibrinolysis. It binds to the plasminogen lysine-binding site and prevents plasminogen binding to its substrate fibrin. They also prevent plasmin degradation of platelet glycoprotein lb receptors, thus preserving platelet function.
In patients undergoing CABG, Myles et al. found that the local fibrinolytic activity in the pericardial cavity significantly exceeded that in the systemic circulation. In patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Siotou et al. have found that plasminogen activators released from the oral and nasal mucosa during craniofacial surgery cause excessive local fibrinolysis and perioperative bleeding. The results of the study showed that antifibrinolytics can significantly reduce blood loss in craniofacial surgical procedures including pediatric craniosynostosis and adult rhinoplasties and in orthognathic surgical procedures, as well as transfusion requirements in pediatric craniofacial surgical procedures. Based on this evidence, we can theorize that topical application of antifibrinolytics can possibly reduce surgical blood loss by the inhibition of local fibrinolysis.
At therapeutic range of 10–16 mg/ml, the commonly reported (≥1%–<10%) complications in association with tranexamic acid were renal, cardiac, respiratory, thoracic, and mediastinal disorders. In high risk procedures, the risk of patients experiencing an adverse event was 3-fold greater in the tranexamic acid-treated patients. The majority of renal disorders reported in published studies were renal dysfunction and renal failure. Renal disorders occurred more frequently in patients undergoing high-risk surgery. The most commonly reported adverse events were cardiogenic shock and myocardial infarction. The most commonly reported central nervous system disorder reported in published studies is stroke. Rare side effects (≥0.01–<0.1%): convulsion, dizziness, chromatopsia, visual impairment embolism, and hypotension (after fast injection).
Split thickness graft take in both the groups were comparable. Average graft take in Group A was 199.8 cm2 and in Group B was 206.2 cm2 which is comparable with P = 0.586 which shows it is comparable, average skin graft take was 92% in both the group. None of the cases in both the groups had subgraft hematoma leading to graft loss [Figure 6] and [Figure 7].
|Figure 6: Bilateral thing burn wound postoperative picture showing split skin graft (SSG) take|
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| Conclusion|| |
Perioperative bleeding is a potential complication of major surgical procedures that increases morbidity and mortality. The invasive and costly nature of interventions, a limited blood supply, and the risk to the patient when bleeding occurs have prompted clinicians to identify effective strategies for bleeding prevention.
We conclude that the use of Tranexamic acid is effective and safe to use for topical use in concentration of 0.5% for reduction of blood loss in burn wound excision. It is further affirmed that this method of drug delivery is both “target-directed” and “potentially safe” to reduce postoperative bleeding. The limitation of our study is its limited sample size and we recommend further authentication by a randomized control study with adequate sample size.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]