Tranexamic Acid In Traumatic Brain Injury Research Articles

Tranexamic acid in patients with traumatic brain injury: a meta-analysis

BackgroundWe performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). MethodsWe 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. ResultsIn 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. ConclusionsEarly 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.

Efecto del ácido tranexámico en sujetos con lesión cerebral traumática: metaanálisis

BackgroundWe performed a meta-analysis to assess the effectiveness and safety of tranexamic acid in patients with traumatic brain injury (TBI). MethodsWe 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. ResultsIn patients with TBI, early administration of TXA was associated with a greater relative benefit (MD - 2.45; 95% CI = - 4.78- - 0.12; p = 0.04) and less total haematoma expansion (MD - 2.52; 95% CI = - 4.85- - 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. ConclusionsEarly 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.

Appraising the use of tranexamic acid in traumatic and non-traumatic intracranial hemorrhage: A narrative review.

Recently there has been increasing interest and debate on the use of tranexamic acid (TXA), an antifibrinolytic drug, in both traumatic and non‐traumatic intracranial hemorrhage. In this review we aim to discuss recent investigations looking at TXA in traumatic brain injury (TBI) and different categories of spontaneous intracranial hemorrhage. We also discuss differences between setting (hospital vs pre‐hospital), dosing and timing strategies, and other logistical challenges surrounding optimal use of TXA for isolated intracranial hemorrhage. Last, we hope to provide guidance for clinicians when considering the use of TXA in a patient with traumatic or non‐traumatic intracranial hemorrhage based on appraisal of the available literature as well as some potential ideas for future research in this area.

Tranexamic acid for traumatic brain injury? Old drug raises new debate

Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and young adults, but also an important medical problem concerning the older part of the population. TBI has an inauspicious prognosis and the mortality remains high, reaching up to 40% in severe injuries. Extensive research on treatment options that could minimize the mortality rate and the number of complications is ongoing and one of these options is tranexamic acid. One of the pathomechanisms of uncontrollable bleeding is hyperfibrinolysis, where the mechanisms controlling fibrinolysis are disrupted and cause it to become excessively intensified. Tranexamic acid (TXA) is an inhibitor of plasminogen and thus inhibits fibrinolysis. This paper aims to provide an overview of the current state of knowledge about tranexamic acid in traumatic brain injury. According to available, data pre-hospital intravenous tranexamic acid infusion administered early, within 3 hours from the injury, seems to reduce mortality in patients with mild to moderate traumatic brain injury, but in patients with severe TBI, this treatment could be associated with increased mortality. The use of TXA does not increase the risk of adverse events. Moreover, the safety of tranexamic acid has been confirmed and no correlation between the use of TXA and a higher incidence of thromboembolic events has been found. Current findings do not give a conclusive answer on the effectiveness of TXA in TBI. Large, international randomized clinical trials have to be performed to answer this question. Additionally, further studies in the use of TXA in TBI in the pediatric population are also needed.

Effect of tranexamic acid on intracranial haemorrhage and infarction in patients with traumatic brain injury: a pre-planned substudy in a sample of CRASH-3 trial patients

BackgroundEarly tranexamic acid (TXA) treatment reduces head injury deaths after traumatic brain injury (TBI). We used brain scans that were acquired as part of the routine clinical practice during the...

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan.

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) versus placebo on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA versus placebo on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite "poor" outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan.

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intracranial bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and new cerebral infarcts up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using absolute measures (ANCOVA) and relative measures (ratios). The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. If any missing post-randomisation scans appear to be missing not at random, we will conduct sensitivity analyses to explore the implications. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients

Tranexamic acid (TXA) is one of the debated therapies in the management of traumatic brain injury (TBI). We conducted this study to evaluate the benefits of TXA in TBI on the mortality and its safety in these patients. This was a prospective randomized open-label trial including all patients, aged at 18years or older, hospitalized in the emergency room during a 13-month period, for TBI. After the realization of the body CT scan, the patients were included if they had intracranial bleeding, and were then randomized according to their medical file number to receive or not the TXA. The eligibility criteria were based on the uncertainty principle, patients with significant extracranial bleeding were excluded since there was evidence that TXA improve their outcome. We enrolled 180 patients aged at 42 ± 20years, with an 88% men-proportion. Subarachnoid haemorrhage was the most frequent lesion in the brain CT-scan (67.5%). After randomization, 96 patients were in the TXA group (53%). Demographic data, clinical, biological and radiological features were statistically comparable in the two groups of patients ('TXA' and 'noTXA'). The needs of transfusion or neurosurgery, the mortality rate, the in-hospital length of stay and the dependency at 28-post-traumatic day were similar in the two groups of patients. However, pulmonary embolism was statistically more frequent in 'TXA' group (11.5 versus 2.4%, p = 0.02). TXA is an interesting treatment in haemorrhagic shock. Its efficiency in head trauma is still debated and controversial. Its impact on the mortality and the needs of transfusion or surgery were not demonstrated in this study. Nevertheless, its safety worth to be studied in larger samples as we found a higher rate of pulmonary embolism in the treated group.