Dataset Information

The effect of prehospital tranexamic acid on outcome in polytrauma patients with associated severe brain injury

ABSTRACT:

Introduction

Tranexamic acid (TXA) has shown to be beneficial in selected patients with hemorrhagic shock. Recently, TXA has gained interest in isolated traumatic brain injury (TBI) patients with variable results. There are limited data on TXA in polytrauma with associated TBI. This study investigated the role of TXA in severely injured patients with associated severe TBI.

Methods

A 7.5-year prospective cohort study was performed to investigate the relation between prehospital TXA and mortality in consecutive trauma patients with associated severe TBI (Abbreviated Injury Scale (AIS)head ≥ 3) admitted to a Level-1 Trauma Center ICU. Indication for prehospital TXA administration was (suspicion of) hemorrhagic shock, and/or systolic blood pressure (SBP) ≤ 90 mmHg. Demographics, data on physiology, resuscitation, and outcomes were prospectively collected.

Results

Two hundred thirty-four patients (67% males) with median age of 49 years and ISS 33 (98% blunt injuries) were included. Thirteen patients (6%) developed thromboembolic complications; mortality rate was 24%. Fifty-one percent of patients received prehospital TXA. TXA patients were younger, had more deranged physiology on arrival, and received more crystalloids and blood products ≤ 24 h. There was, however, no difference in overall outcome between TXA patients and no-TXA patients.

Conclusions

Despite having a more deranged physiology TXA patients had similar outcome compared to no-TXA patients who were much older. Thromboembolic complication rate was low. Prehospital tranexamic acid has no evident effect on outcome in polytrauma patients with associated critical brain injury.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00068-021-01827-5.

SUBMITTER: van Wessem K

PROVIDER: S-EPMC8590807 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe development and expansion of intracranial hematoma are associated with adverse outcomes. Use of tranexamic acid might limit intracranial hematoma formation, but its association with outcomes of severe traumatic brain injury (TBI) is unclear.ObjectiveTo assess whether prehospital administration of tranexamic acid is associated with mortality and functional outcomes in a group of patients with severe TBI.Design, setting, and participantsThis multicenter cohort study is an analysis of prospectively collected observational data from the Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma (BRAIN-PROTECT) study in the Netherlands. Patients treated for suspected severe TBI by the Dutch Helicopter Emergency Medical Services between February 2012 and December 2017 were included. Patients were followed up for 1 year after inclusion. Data were analyzed from January 10, 2020, to September 10, 2020.ExposuresAdministration of tranexamic acid during prehospital treatment.Main outcomes and measuresThe primary outcome was 30-day mortality. Secondary outcomes included mortality at 1 year, functional neurological recovery at discharge (measured by Glasgow Outcome Scale), and length of hospital stay. Data were also collected on demographic factors, preinjury medical condition, injury characteristics, operational characteristics, and prehospital vital parameters.ResultsA total of 1827 patients were analyzed, of whom 1283 (70%) were male individuals and the median (interquartile range) age was 45 (23-65) years. In the unadjusted analysis, higher 30-day mortality was observed in patients who received prehospital tranexamic acid (odds ratio [OR], 1.34; 95% CI, 1.16-1.55; P < .001), compared with patients who did not receive prehospital tranexamic acid. After adjustment for confounders, no association between prehospital administration of tranexamic acid and mortality was found across the entire cohort of patients. However, a substantial increase in the odds of 30-day mortality persisted in patients with severe isolated TBI who received prehospital tranexamic acid (OR, 4.49; 95% CI, 1.57-12.87; P = .005) and after multiple imputations (OR, 2.05; 95% CI, 1.22-3.45; P = .007).Conclusions and relevanceThis study found that prehospital tranexamic acid administration was associated with increased mortality in patients with isolated severe TBI, suggesting the judicious use of the drug when no evidence for extracranial hemorrhage is present.

Project description:BACKGROUND:Patients with isolated traumatic brain injury (TBI) are likely to benefit from effective prehospital care to prevent secondary brain injury. Only a few studies have focused on the impact of advanced interventions in TBI patients by prehospital physicians. The primary end-point of this study was to assess the possible effect of an on-scene anaesthetist on mortality of TBI patients. A secondary end-point was the neurological outcome of these patients. METHODS:Patients with severe TBI (defined as a head injury resulting in a Glasgow Coma Score of ?8) from 2005 to 2010 and 2012-2015 in two study locations were determined. Isolated TBI patients transported directly from the accident scene to the university hospital were included. A modified six-month Glasgow Outcome Score (GOS) was defined as death, unfavourable outcome (GOS 2-3) and favourable outcome (GOS 4-5) and used to assess the neurological outcomes. Binary logistic regression analysis was used to predict mortality and good neurological outcome. The following prognostic variables for TBI were available in the prehospital setting: age, on-scene GCS, hypoxia and hypotension. As per the hypothesis that treatment provided by an on-scene anaesthetist would be beneficial to TBI outcomes, physician was added as a potential predictive factor with regard to the prognosis. RESULTS:The mortality data for 651 patients and neurological outcome data for 634 patients were available for primary and secondary analysis. In the primary analysis higher age (OR 1.06 CI 1.05-1.07), lower on-scene GCS (OR 0.85 CI 0.79-0.92) and the unavailability of an on-scene anaesthetist (OR 1.89 CI 1.20-2.94) were associated with higher mortality together with hypotension (OR 3.92 CI 1.08-14.23). In the secondary analysis lower age (OR 0.95 CI 0.94-0.96), a higher on-scene GCS (OR 1.21 CI 1.20-1.30) and the presence of an on-scene anaesthetist (OR 1.75 CI 1.09-2.80) were demonstrated to be associated with good patient outcomes while hypotension (OR 0.19 CI 0.04-0.82) was associated with poor outcome. CONCLUSION:Prehospital on-scene anaesthetist treating severe TBI patients is associated with lower mortality and better neurological outcome.

Project description:Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA's various sites and modes of action may further improve patient outcomes.

Project description:ImportanceTraumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI.ObjectiveTo determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI.Design, setting, and participantsMulticenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher.InterventionsThree interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309).Main outcomes and measuresThe primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events.ResultsAmong 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16).Conclusions and relevanceAmong patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended.Trial registrationClinicalTrials.gov Identifier: NCT01990768.

Project description:IntroductionHaemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysisThe Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5-8) and unfavourable (GOSE 1-4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and disseminationThe study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration numberNCT02187120.

Project description:ObjectiveTo assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.MethodsA nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.InterventionsPatients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.Main outcome measuresIntracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.ResultsOf the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).ConclusionsThis trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population. Trial registration ISRCTN86750102.