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Tranexamic acid in patients with traumatic brain injury: A meta-analysis
Sarhan Boshra, R. M., Abdelrahim, M. E. A., Osama, H.
Revista espanola de anestesiologia y reanimacion. 2024
Abstract
BACKGROUND We performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). METHODS We searched the literature for articles evaluating the effectiveness and safety of tranexamic acid (TXA) in TBI published between January 2012 and January 2021, and identified 8 studies with a total of 10860 patients: 5660 received TXA and 5200 served as controls. We used a dichotomous or continuous approach with a random or fixed-effect model to assess the efficacy and safety of TXA in TBI, and calculated the mean difference (MD) and odds ratio (OR) with the corresponding 95% confidence interval. RESULTS In patients with TBI, early administration of TXA was associated with a greater relative benefit (MD -2.45; 95% CI = -4.78 to -0.12; p = 0.04) and less total haematoma expansion (MD - 2.52; 95% CI = -4.85 to -0.19; p = 0.03) compared to controls. There were no statistically significant differences in mortality (OR 0.94; 95% CI = 0.85-1.03; p = 0.18), presence of progressive haemorrhage (OR 0.75; 95% CI = 0.56-1.01; p = 0.06), need for neurosurgery (OR 1.15; 95% CI = 0.66-1.98; p = 0.63), high Disability Rating Scale score (OR 0.90; 95% CI = 0.56-1.45; p = 0.68), and incidence of ischaemic or thromboembolic complications (OR 1.34; 95% CI = 0.33-5.46; p = 0.68) between TBI patients treated with TXA and controls. CONCLUSIONS Early administration of TXA in TBI patients may have a greater relative benefit and may inhibit haematoma expansion. There were no significant differences in mortality, presence of progressive haemorrhage, need for neurosurgery, high Disability Rating Scale score, and incidence of ischaemic or thromboembolic complications between TBI patients treated with TXA and controls. Further studies are needed to validate these results.
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Effectiveness of Tranexamic Acid in Trauma Patients: A Systematic Review
Meza Monge, K., Domene, S. S., Diaz Mendoza, D. L., Vidal-Gallardo, A., Alfaro Llique, A. M., Rodriguez, M., Premchandra, P., Anwar Pandya, S., Arruarana, V. S., Aleman Paredes, K., et al
Cureus. 2024;16(1):e52111
Abstract
Tranexamic acid (TXA), a fibrinolytic agent, effectively inhibits plasminogen activation, thereby reducing fibrinolysis and hemorrhage. This study focused on its application in trauma patients undergoing emergency surgery, a critical area due to trauma's significant role in mortality. Our investigation involved a meticulous screening of randomized controlled trials from databases including Scopus, PubMed, Web of Science, and Cochrane. The findings indicate that TXA intervention is promising in enhancing outcomes for trauma patients. However, the drug's effectiveness may vary based on the specific nature of the medical condition. In summary, robust evidence suggests that TXA can diminish blood loss, lower transfusion rates, reduce complications, and improve hemoglobin and hematocrit levels in surgical patients. Consequently, TXA should be considered a crucial medication, readily available to mitigate morbidity and mortality in surgical settings. Future research should explore factors influencing TXA's effectiveness in traumatic brain injury cases and across a broad spectrum of surgical scenarios in diverse patient populations. This would further guide clinicians in refining and optimizing the use of TXA.
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Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials
Fouche, P. F., Stein, C., Nichols, M., Meadley, B., Bendall, J. C., Smith, K., Anderson, D., Doi, S. A.
Annals of emergency medicine. 2023
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Editor's Choice
Abstract
STUDY OBJECTIVE Traumatic injury causes a significant number of deaths due to bleeding. Tranexamic acid (TXA), an antifibrinolytic agent, can reduce bleeding in traumatic injuries and potentially enhance outcomes. Previous reviews suggested potential TXA benefits but did not consider the latest trials. METHODS A systematic review and bias-adjusted meta-analysis were performed to assess TXA's effectiveness in emergency traumatic injury settings by pooling estimates from randomized controlled trials. Researchers searched Medline, Embase, and Cochrane Central for randomized controlled trials comparing TXA's effects to a placebo in emergency trauma cases. The primary endpoint was 1-month mortality. The methodological quality of the trials underwent assessment using the MASTER scale, and the meta-analysis applied the quality-effects method to adjust for methodological quality. RESULTS Seven randomized controlled trials met the set criteria. This meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84 to 0.95) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76, 95% CI 0.65 to 0.88) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96, 95% CI 0.73 to 1.27). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus inhospital. CONCLUSIONS This synthesis demonstrates that TXA use for trauma in emergencies leads to a reduction in 1-month mortality, with no significant evidence of problematic vascular occlusive events. Administering TXA in the out-of-hospital setting is associated with reduced mortality compared to inhospital administration, and less mortality with TXA in systemic trauma is noted compared with traumatic brain injury specifically.
PICO Summary
Population
Patients with traumatic injuries in emergency settings (7 randomised controlled trials).
Intervention
Tranexamic acid (TXA).
Comparison
Placebo.
Outcome
The primary endpoint was 1-month mortality. The meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89; 95% confidence interval (CI) [0.84, 0.95]) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76; 95% CI [0.65, 0.88]) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96; 95% CI [0.73, 1.27]). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus in-hospital.
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Factors that influence the administration of tranexamic acid (TXA) to trauma patients in prehospital settings: a systematic review
Nicholson, H., Scotney, N., Briscoe, S., Kirby, K., Bedson, A., Goodwin, L., Robinson, M., Taylor, H., Thompson Coon, J., Voss, S., et al
BMJ open. 2023;13(5):e073075
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Editor's Choice
Abstract
OBJECTIVE In the UK there are around 5400 deaths annually from injury. Tranexamic acid (TXA) prevents bleeding and has been shown to reduce trauma mortality. However, only 5% of UK major trauma patients who are at risk of haemorrhage receive prehospital TXA. This review aims to examine the evidence regarding factors influencing the prehospital administration of TXA to trauma patients. DESIGN Systematic literature review. DATA SOURCES AMED, CENTRAL, CINAHL, Cochrane Database of Systematic Reviews, Conference Proceedings Citation Index-Science, Embase and MEDLINE were searched from January 2010 to 2020; searches were updated in June 2022. CLINICALTRIALS gov and OpenGrey were also searched and forward and backwards citation chasing performed. ELIGIBILITY CRITERIA All primary research reporting factors influencing TXA administration to trauma patients in the prehospital setting was included. DATA EXTRACTION AND SYNTHESIS Two independent reviewers performed the selection process, quality assessment and data extraction. Data were tabulated, grouped by setting and influencing factor and synthesised narratively. RESULTS Twenty papers (278 249 participants in total) were included in the final synthesis; 13 papers from civilian and 7 from military settings. Thirteen studies were rated as 'moderate' using the Effective Public Health Practice Project Quality Assessment Tool. Several common factors were identified: knowledge and skills; consequences and social influences; injury type (severity, injury site and mechanism); protocols; resources; priorities; patient age; patient sex. CONCLUSIONS This review highlights an absence of high-quality research. Preliminary evidence suggests a host of system and individual-level factors that may be important in determining whether TXA is administered to trauma patients in the prehospital setting. FUNDING AND REGISTRATION This review was supported by Research Capability Funding from the South Western Ambulance Service NHS Foundation Trust and the National Institute for Health Research Applied Research Collaboration South West Peninsula. PROSPERO REGISTRATION NUMBER CRD42020162943.
PICO Summary
Population
Any trauma patients in prehospital settings (20 studies, n= 278,249).
Intervention
Exposure: Factors influencing the decision to administer tranexamic acid (TXA).
Comparison
Outcome
This systematic review included 13 studies from civilian settings and 7 studies from military settings. This review highlighted a lack of high-quality research addressing the factors that influence prehospital TXA administration, particularly in children or patients with isolated head injuries. Common factors identified suggested a host of system and individual-level factors including: knowledge and skills, consequences and social influences, injury type (including severity, injury site and mechanism of injury), protocols, resources, priorities, patient age, and patient sex.
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The Efficacy of Tranexamic Acid for the Treatment of Traumatic Hip Fractures: A Network Meta-Analysis
Bloom DA, Lin CC, Manzi JE, Mojica ES, Telgheder ZL, Chapman CB
Journal of orthopaedic trauma. 2023
Abstract
OBJECTIVES Network meta-analysis to compare the efficacy of different dosages of intravenous(IV) acid(TXA) in the treatment of traumatic hip fractures against the control group of no TXA. DATA SOURCES This study utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform a network meta-analysis on the use of TXA for the treatment of hip fractures. The study team utilized Ovid MEDLINE, Cochrane Reviews, Scopus, Embase, and Web of Science databases to perform the search. Studies were selected that were published in English between the years 2010 and 2020. STUDY SELECTION/DATA EXTRACTION For inclusion in this study, selected manuscripts were required to be randomized controlled trials with at least one control group had no anti-fibrinolytic intervention to serve as a control, IV formulations of TXA were utilized as part of the treatment group. Furthermore, all study participants must have undergone surgical intervention for traumatic hip fractures. Studies that did not immediately meet criteria for inclusion were saved for review by the full investigating team and were included based on consensus. DATA SYNTHESIS All statistical analyses conducted for this study were performed using R (R Foundation for Statistical Computing, Vienna, Austria). Network meta-analyses were conducted with a frequentist approach with a random effects model using the netmeta package version 0.9-6 in R. The frequentist equivalent to surface under the cumulative ranking (SUCRA) probabilities, termed "P-Score" was used to rank different treatments. CONCLUSION The use of TXA in the surgical management of traumatic hip fractures reduces the number of transfusions and perioperative blood loss, with minimal to no increased incidence of thrombotic events when compared to control. When comparing formulations, no route of administration is clearly superior in reducing perioperative blood loss.
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A Systematic Review and Meta-Analysis of Sample Size Methodology for Traumatic Hemorrhage Trials
Ghossein J, Fernando SM, Rochwerg B, Inaba K, Lampron J, Tran A
The journal of trauma and acute care surgery. 2023
Abstract
BACKGROUND Trauma hemorrhage remains the most common cause of preventable mortality in trauma. In order to guide clinical practice, RCTs provide high-quality evidence to inform clinical decision making. The clinical relevance and inferences made by RCTs are dependent on assumptions made during sample size calculation. METHODS To describe the quality of methodology for sample size determination, we conducted a systemic review RCTs evaluating interventions that aim to improve survival in adults with trauma related hemorrhage. Estimated and actual outcome data is compared, including components of sample size determination. RESULTS A total of 13 RCTs were included. We noted a high rate of negative trial results (11 of 13 studies). Most studies were multi-center and conducted in North America, evaluating patients with blunt and penetrating injuries. The criteria for hemorrhagic shock varied across studies. All studies did not accurately estimate the mortality rate during sample size calculation. All but one study overestimated the mortality reduction during sample size calculation; the median absolute mortality reduction was 3%, compared to a target of 10%. Only the CRASH-2 study used a minimal clinically important different for treatment effect target. No RCTs employed prognostic enrichment. Most studies were terminated (8 of 13), mainly for futility. CONCLUSIONS Taken together, this review highlights that current clinical trial methodology is limited by imprecise control group risk estimates, overly optimistic treatment effect estimates and lack of transparent justification for such targets. These limitations result in studies at high risk for futility and potentially premature abandonment of promising therapies. Given the high morbidity and mortality of trauma-related hemorrhage, we recommend that future conduct of trauma RCTs incorporate 1) prognostic enrichment to inform baseline risk, (2) justify target treatment differences based on clinical importance and realistic estimates of feasibility, and (3) be transparent and provide justification for the assumptions made. LEVEL OF EVIDENCE Systematic Review/Meta Analysis; Level II.
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Efficacy of high dose tranexamic acid (TXA) for hemorrhage: A systematic review and meta-analysis
Hmidan Simsam M, Delorme L, Grimm D, Priestap F, Bohnert S, Descoteaux M, Hilsden R, Laverty C, Mickler J, Parry N, et al
Injury. 2023
Abstract
BACKGROUND Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. METHODS We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). CONCLUSION When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. LEVEL OF EVIDENCE Systematic review and meta-analysis, level IV.
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Effectiveness and safety of tranexamic acid in pediatric trauma: A systematic review and meta-analysis
Kornelsen, E., Kuppermann, N., Nishijima, D. K., Ren, L. Y., Rumantir, M., Gill, P. J., Finkelstein, Y.
The American Journal of Emergency Medicine. 2022;55:103-110
Abstract
OBJECTIVE Trauma is the leading cause of childhood death in the United States. Our goal was to determine the effectiveness of tranexamic acid (TXA) in improving survival in pediatric trauma. METHODS MEDLINE (OVID), Embase (OVID), Cochrane Central Register databases, CINAHL (EBSCO), Web of Science (Clarivate Analytics), and grey literature sources were searched for publications reporting survival and safety outcomes in children receiving TXA in acute trauma, with no language restrictions, published until February 11, 2021. Two independent researchers assessed studies for eligibility, bias, and quality. Data on the study setting, injury type, participants, design, interventions, TXA dosing and outcomes were extracted. The primary outcome was survival in children who received TXA following trauma. Forest plots of effect estimates were constructed for each study. Heterogeneity was assessed and data were pooled by meta-analysis using a random-effects model. RESULTS Fourteen articles met inclusion criteria - six single-institution and eight multicentre retrospective cohort studies. Overall, TXA use was not associated with increased survival in pediatric trauma (adjusted odds ratio [aOR]: 0.61, 95% CI: 0.30-1.22) after adjustment for patient-level variables, such as injury severity. Increased survival was documented in the subset of children experiencing trauma in combat settings (aOR for mortality: 0.31, 95% CI: 0.14-0.68). There were no differences in the odds of thromboembolic events (OR 1.15, 95% CI: 0.46-2.87) in children who received TXA versus not. CONCLUSIONS The utility of TXA in children with trauma is unclear. Guidelines supporting TXA use in pediatric trauma may not be based on the available evidence of its use in this context. Rigorous trials measuring survival and other meaningful outcomes and exploring optimal TXA dosing are urgently needed. Study Registration (PROSPERO): CRD42020157683.
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Association of Tranexamic Acid Administration With Mortality and Thromboembolic Events in Patients With Traumatic Injury: A Systematic Review and Meta-analysis
Karl V, Thorn S, Mathes T, Hess S, Maegele M
JAMA network open. 2022;5(3):e220625
Abstract
IMPORTANCE Tranexamic acid is widely available and used off-label in patients with bleeding traumatic injury, although the literature does not consistently agree on its efficacy and safety. OBJECTIVE To examine the association of tranexamic acid administration with mortality and thromboembolic events compared with no treatment or with placebo in patients with traumatic injury in the literature. DATA SOURCES On March 23, 2021, PubMed, Embase, and the Cochrane Library were searched for eligible studies published between 1986 and 2021. STUDY SELECTION Randomized clinical trials and observational studies investigating tranexamic acid administration compared with no treatment or placebo among patients with traumatic injury and traumatic brain injury who were 15 years or older were included. Included studies were published in English or German. The electronic search yielded 1546 records, of which 71 were considered for full-text screening. The selection process was performed independently by 2 reviewers. DATA EXTRACTION AND SYNTHESIS The study followed the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted by 2 independent reviewers and pooled using the inverse-variance random-effects model. MAIN OUTCOMES AND MEASURES Outcomes were formulated before data collection and included mortality at 24 hours and 28 and 30 days (1 month) as well as the incidence of thromboembolic events and the amount of blood products administered. Owing to missing data, overall mortality was added and the amount of blood products administered was discarded. RESULTS Thirty-one studies with a total of 43 473 patients were included in the systematic review. The meta-analysis demonstrated that administration of tranexamic acid was associated with a significant decrease in 1-month mortality compared with the control cohort (risk ratio, 0.83 [95% CI, 0.71-0.97]; I2 = 35%). The results of meta-analyses for 24-hour and overall mortality and thromboembolic events were heterogeneous and could not be pooled. Further investigations on clinical heterogeneity showed that populations with trauma and trial conditions differed markedly. CONCLUSIONS AND RELEVANCE These findings suggest that tranexamic acid may be beneficial in various patient populations with trauma. However, reasonable concerns about potential thromboembolic events with tranexamic acid remain.
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Systemic hemostatic agents initiated in trauma patients in the pre-hospital setting: a systematic review
Biffi A, Porcu G, Castellini G, Napoletano A, Coclite D, D'Angelo D, Fauci AJ, Iacorossi L, Latina R, Salomone K, et al
European journal of trauma and emergency surgery : official publication of the European Trauma Society. 2022
Abstract
PURPOSE The effect of systemic hemostatic agents initiated during pre-hospital care of severely injured patients with ongoing bleeding or traumatic brain injury (TBI) remains controversial. A systematic review and meta-analysis was therefore conducted to assess the effectiveness and safety of systemic hemostatic agents as an adjunctive therapy in people with major trauma and hemorrhage or TBI in the context of developing the Italian National Institute of Health guidelines on major trauma integrated management. METHODS PubMed, Embase, and Cochrane Library databases were searched up to October 2021 for studies that investigated pre-hospital initiated treatment with systemic hemostatic agents. The certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach, and the quality of each study was determined with the Cochrane risk-of-bias tool. The primary outcome was overall mortality, and secondary outcomes included cause-specific mortality, health-related quality of life, any adverse effects and blood product use, hemorrhage expansion, and patient-reported outcomes. RESULTS Five trials of tranexamic acid (TXA) met the inclusion criteria for this meta-analysis. With a high certainty of evidence, when compared to placebo TXA reduced mortality at 24 h (relative risk = 0.83, 95% confidence interval = 0.73-0.94) and at 1 month among trauma patients (0.91, 0.85-0.97). These results depend on the subgroup of patients with significant hemorrhage because in the subgroup of TBI there are no difference between TXA and placebo. TXA also reduced bleeding death and multiple organ failure whereas no difference in health-related quality of life. CONCLUSION Balancing benefits and harms, TXA initiated in the pre-hospital setting can be used for patients experiencing major trauma with significant hemorrhage since it reduces the risk of mortality at 24 h and one month with no difference in terms of adverse effects when compared to placebo. Considering the subgroup of severe TBI, no difference in mortality rate was found at 24 h and one month. These results highlight the need to conduct future studies to investigate the role of other systemic hemostatic agents in the pre-hospital settings.