1.
Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury
Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, Bulger EM, Idris AH, Christenson J, Morrison LJ, et al
Jama. 2020;324(10):961-974
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Abstract
IMPORTANCE Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. OBJECTIVE To 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 PARTICIPANTS Multicenter, 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. INTERVENTIONS Three 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 MEASURES The 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. RESULTS Among 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 RELEVANCE Among 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 REGISTRATION ClinicalTrials.gov Identifier: NCT01990768.
PICO Summary
Population
Out-of-hospital patients with traumatic brain injury aged 15 years or older (n= 1280).
Intervention
Bolus maintenance group: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (n = 312).
Comparison
Bolus only group: out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (n = 345). Placebo group: out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (n = 309).
Outcome
A total of 819 participants were available for primary outcome analysis at 6-month follow-up. The primary outcome (favorable neurologic function at 6 months) occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group. There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%); 6-month Disability Rating Scale score (6.8 vs 7.6); or progression of intracranial hemorrhage (16% vs 20%).
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The effect of massive transfusion protocol implementation on the survival of trauma patients: a systematic review and meta-analysis
Consunji R, Elseed A, El-Menyar A, Sathian B, Rizoli S, Al-Thani H, Peralta R
Blood transfusion = Trasfusione del sangue. 2020
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Editor's Choice
Abstract
BACKGROUND Massive transfusion protocol (MTP) has been widely adopted for the care of bleeding trauma patients but its actual effectiveness is unclear. An earlier meta-analysis on the implementation of MTP for injured patients from 1990 to 2013 reported that only 2 out of 8 studies showed statistical improvement in survival. This study aimed to conduct an updated systematic review and meta-analysis to evaluate the effect of implementing an MTP on the mortality of trauma patients. MATERIALS AND METHODS MEDLINE, PubMed, Cochrane Library and Google scholar databases were systematically searched for relevant studies published from 1(st) January 2008 to 30(th) September 2019 using a combination of keywords and additional manual searching of reference lists. Inclusion criteria were: original study in English, study population including trauma patients, and comparison of mortality outcomes before and after institutional implementation of an MTP. Primary outcomes were 24-hour, 30-day, and overall mortality. RESULTS Fourteen studies met inclusion criteria, analysing outcomes from 3,201 trauma patients. There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients (OR 0.71 [0.56-0.90]). No significant reduction was seen in either the 24-hour mortality (OR 0.81 [0.57-1.14]) or the 30-day mortality (OR 0.73 [0.46-1.16]). However, when mortality timing was unspecified, mortality was statistically reduced (OR 0.69 [0.55-0.86]). DISCUSSION The present study found a significant reduction in mortality following MTP implementation and thus it should be recommended to all institutions managing acutely injured patients. To better identify which elements of an MTP contribute to this effect, we encourage the use of standard nomenclature, indicators, protocols and patient populations in all future MTP studies.
PICO Summary
Population
Trauma patients (14 studies, n= 3201).
Intervention
Implementation of a massive transfusion protocol (MTP) on the mortality of trauma patients.
Comparison
Outcome
There was a wide range of outcomes, patient populations, and process indicators utilised by the different authors. MTP significantly reduced the overall mortality for trauma patients. No significant reduction was seen in either the 24-hour mortality or the 30-day mortality. However, when mortality timing was unspecified, mortality was statistically reduced.