The effect of intravenous tranexamic acid on preventing the progress of cerebral hemorrhage in patients with brain traumatic injuries compared to placebo: A randomized clinical trial
“…The minimum age of the participants was greater than 15 years, which included both adults and adolescents. The timing of TXA administration varied among studies, with five trials in which the post-traumatic registration time was less than 3 h [ 13 , 15 , 17 , 19 , 25 ], seven trials in which the post-traumatic registration time was more than 3 h [ 14 , 16 , 18 , 19 , 21 , 26 , 27 ], and one article that did not clearly explain the registration time. In the included trials, the TXA dose was mostly similar, and the most common regimen was a loading dose of 1 g, followed by a maintenance dose of 1 g over 8 h [ 13 – 22 , 25 – 27 ].…”
Section: Resultsmentioning
confidence: 99%
“…9 ). Two articles [ 17 , 19 ] showed that TXA was a protective factor for mean hemorrhage volume, and three [ 16 , 20 , 21 ] showed that TXA was not associated with mean hemorrhage volume. Fig.…”
Objective
Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment.
Methods
PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence.
Results
Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92–1.06), adverse events (RR 0.93, 95% Cl 0.76–1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94–1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82–1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89–1.38), or rebleeding (RR 0.97, 95% Cl 0.82–1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]).
Conclusion
TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out.
Trial registration
The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).
“…The minimum age of the participants was greater than 15 years, which included both adults and adolescents. The timing of TXA administration varied among studies, with five trials in which the post-traumatic registration time was less than 3 h [ 13 , 15 , 17 , 19 , 25 ], seven trials in which the post-traumatic registration time was more than 3 h [ 14 , 16 , 18 , 19 , 21 , 26 , 27 ], and one article that did not clearly explain the registration time. In the included trials, the TXA dose was mostly similar, and the most common regimen was a loading dose of 1 g, followed by a maintenance dose of 1 g over 8 h [ 13 – 22 , 25 – 27 ].…”
Section: Resultsmentioning
confidence: 99%
“…9 ). Two articles [ 17 , 19 ] showed that TXA was a protective factor for mean hemorrhage volume, and three [ 16 , 20 , 21 ] showed that TXA was not associated with mean hemorrhage volume. Fig.…”
Objective
Tranexamic acid (TXA) plays a significant role in the treatment of traumatic diseases. However, its effectiveness in patients with traumatic brain injury (TBI) seems to be contradictory, according to the recent publication of several meta-analyses. We aimed to determine the efficacy of TXA treatment at different times and doses for TBI treatment.
Methods
PubMed, MEDLINE, EMBASE, Cochrane Library, and Google Scholar were searched for randomized controlled trials that compared TXA and a placebo in adults and adolescents (≥ 15 years of age) with TBI up to January 31, 2022. Two authors independently abstracted the data and assessed the quality of evidence.
Results
Of the identified 673 studies, 13 involving 18,675 patients met our inclusion criteria. TXA had no effect on mortality (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.92–1.06), adverse events (RR 0.93, 95% Cl 0.76–1.14), severe TBI (Glasgow Coma Scale score from 3 to 8) (RR 0.99, 95% Cl 0.94–1.05), unfavorable Glasgow Outcome Scale (GOS < 4) (RR 0.96, 95% Cl 0.82–1.11), neurosurgical intervention (RR 1.11, 95% Cl 0.89–1.38), or rebleeding (RR 0.97, 95% Cl 0.82–1.16). TXA might reduce the mean hemorrhage volume on subsequent imaging (standardized mean difference, -0.35; 95% CI [-0.62, -0.08]).
Conclusion
TXA at different times and doses was associated with reduced mean bleeding but not with mortality, adverse events, neurosurgical intervention, and rebleeding. More research data is needed on different detection indexes and levels of TXA in patients with TBI, as compared to those not receiving TXA; although the prognostic outcome for all harm outcomes was not affected, the potential for harm was not ruled out.
Trial registration
The review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42022300484).
“…The data including study design, publication years, types of interventions, and other details are shown in Tables 1 , 2 . The total sample size was 26,956, and the study included 13 interventions, in the order of TXA ( Yutthakasemsunt et al, 2013 ; Chakroun-Walha et al, 2018 ; Collaborators, 2019 ; collaborators et al, 2010 ; Fakharian et al, 2018 ; Mojallal et al, 2020 ; Rowell et al, 2020 ; Perel et al, 2012 ), EPO ( Aloizos et al, 2015 ; Nichol et al, 2015 ; Li et al, 2016 ; Hellewell et al, 2017 ; Bai and Gao, 2018 ; Skrifvars et al, 2018 ), progesterone ( Wright et al, 2007 ; Xiao et al, 2007 ; Xiao et al, 2008 ; Shakeri et al, 2013 ; Skolnick et al, 2014 ; Wright et al, 2014 ; Soltani et al, 2017 ), progesterone + vitamin D ( Aminmansour et al, 2012 ), atorvastatin ( Farzanegan et al, 2017 ), beta-blocker therapy ( Khalili et al, 2020 ), Bradycor ( Marmarou et al, 1999 ), Enoxaparin ( Baharvahdat et al, 2019 ), Tracoprodi ( Yurkewicz et al, 2005 ), dexanabinol ( Maas et al, 2006 ), selenium ( Moghaddam et al, 2017 ), simvastatin ( Shafiee et al, 2021 ) and placebo.…”
Section: Resultsmentioning
confidence: 99%
“…For Baharvahdat et al (2019) , Fakharian et al (2018) , Marmarou et al (1999) , Perel et al (2012) , Shafiee et al (2021) , ( Skolnick et al (2014) , Wright et al (2014) , Xiao et al (2008) ), and Yutthakasemsunt et al (2013) , whether the correct blinding was applied in terms of outcome assessment was uncertain. Hellewell et al (2017) , Moghaddam et al (2017) , Mojallal et al (2020) , Wright et al (2007) , Rowell et al (2020) , and Shakeri et al (2013) did not implement blinding for outcome assessment, and Chakroun-Walha et al (2018) and Khalili et al (2020) did not perform allocation concealment and implement blinding. This indicated that the quality of the randomized controlled studies included in the analysis was moderate ( Figures 2A,B ).…”
Section: Resultsmentioning
confidence: 99%
“…,Perel et al (2012),Shafiee et al (2021),(Skolnick et al (2014),Wright et al (2014),Xiao et al (2008)), andYutthakasemsunt et al (2013), whether the correct blinding was applied in terms of outcome assessment was uncertain Hellewell et al (2017),Moghaddam et al (2017),Mojallal et al (2020),Wright et al (2007),Rowell et al (2020), andShakeri et al (2013). did not implement blinding for outcome assessment, and Chakroun-Walha et al (…”
Objective: This network meta-analysis aimed to explore the effect of different drugs on mortality and neurological improvement in patients with traumatic brain injury (TBI), and to clarify which drug might be used as a more promising intervention for treating such patients by ranking.Methods: We conducted a comprehensive search from PubMed, Medline, Embase, and Cochrane Library databases from the establishment of the database to 31 January 2022. Data were extracted from the included studies, and the quality was assessed using the Cochrane risk-of-bias tool. The primary outcome measure was mortality in patients with TBI. The secondary outcome measures were the proportion of favorable outcomes and the occurrence of drug treatment–related side effects in patients with TBI in each drug treatment group. Statistical analyses were performed using Stata v16.0 and RevMan v5.3.0.Results: We included 30 randomized controlled trials that included 13 interventions (TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, simvastatin, and placebo). The analysis revealed that these drugs significantly reduced mortality in patients with TBI and increased the proportion of patients with favorable outcomes after TBI compared with placebo. In terms of mortality after drug treatment, the order from the lowest to the highest was progesterone + vitamin D, beta-blocker therapy, EPO, simvastatin, Enoxaparin, Bradycor, Tracoprodi, selenium, atorvastatin, TXA, progesterone, dexanabinol, and placebo. In terms of the proportion of patients with favorable outcomes after drug treatment, the order from the highest to the lowest was as follows: Enoxaparin, progesterone + vitamin D, atorvastatin, simvastatin, Bradycor, EPO, beta-blocker therapy, progesterone, Tracoprodi, TXA, selenium, dexanabinol, and placebo. In addition, based on the classification of Glasgow Outcome Scale (GOS) scores after each drug treatment, this study also analyzed the three aspects of good recovery, moderate disability, and severe disability. It involved 10 interventions and revealed that compared with placebo treatment, a higher proportion of patients had a good recovery and moderate disability after treatment with progesterone + vitamin D, Bradycor, EPO, and progesterone. Meanwhile, the proportion of patients with a severe disability after treatment with progesterone + vitamin D and Bradycor was also low.Conclusion: The analysis of this study revealed that in patients with TBI, TXA, EPO, progesterone, progesterone + vitamin D, atorvastatin, beta-blocker therapy, Bradycor, Enoxaparin, Tracoprodi, dexanabinol, selenium, and simvastatin all reduced mortality and increased the proportion of patients with favorable outcomes in such patients compared with placebo. Among these, the progesterone + vitamin D had not only a higher proportion of patients with good recovery and moderate disability but also a lower proportion of patients with severe disability and mortality. However, whether this intervention can be used for clinical promotion still needs further exploration.
Purpose of reviewTraumatic brain injury (TBI) is a leading cause of trauma-related deaths, and pharmacologic interventions to limit intracranial bleeding should improve outcomes. Tranexamic acid reduces mortality in injured patients with major systemic bleeding, but the effects of antifibrinolytic drugs on outcomes after TBI are less clear. We therefore summarize recent evidence to guide clinicians on when (not) to use antifibrinolytic drugs in TBI patients.
Recent findingsTranexamic acid is the only antifibrinolytic drug that has been studied in patients with TBI. Several recent studies failed to conclusively demonstrate a benefit on survival or neurologic outcome. A large trial with more than 12 000 patients found no significant effect of tranexamic acid on head-injury related death, allcause mortality or disability across the overall study population, but observed benefit in patients with mild to moderate TBI. Observational evidence signals potential harm in patients with isolated severe TBI.
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