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1.
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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Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial
Nishijima DK, VanBuren JM, Linakis SW, Hewes HA, Myers SR, Bobinski M, Tran NK, Ghetti S, Adelson PD, Roberts I, et al
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2022
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Editor's Choice
Abstract
BACKGROUND The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. METHODS Severely injured children (0 up to 18(th) birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. RESULTS A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (9 patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. CONCLUSION Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large-scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.
PICO Summary
Population
Severely injured children enrolled in the TIC-TOC trial across four centers in US (n= 31).
Intervention
15 mg/kg of tranexamic acid (TXA) dose, followed by 2 mg/kg/hr infusion (n= 9).
Comparison
30 mg/kg of TXA dose, followed by 4 mg/kg/hr infusion (n= 10). Saline placebo and infusion (n= 12).
Outcome
All patients had their primary outcome measured. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The mean time from injury to randomization was 2.4 hours (SD 0.6 hours). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. No statistically significant differences in any of the clinical outcomes were identified.
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Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial
Crombie N, Doughty HA, Bishop JRB, Desai A, Dixon EF, Hancox JM, Herbert MJ, Leech C, Lewis SJ, Nash MR, et al
The Lancet. Haematology. 2022
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Editor's Choice
Abstract
BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.
PICO Summary
Population
Patients aged 16 years old or older with trauma-related haemorrhagic shock enrolled in the resuscitation with pre-hospital blood products (RePHILL) trial, based across four UK prehospital critical care services (n= 432).
Intervention
Packed red blood cells and lyophilised plasma (PRBC-LyoPlas, n= 209).
Comparison
Sodium chloride (n= 223).
Outcome
The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. The composite primary outcome occurred in 128 (64%) of 199 patients receiving PRBC-LyoPlas and 136 (65%) of 210 receiving sodium chloride. The rates of transfusion-related complications in the first 24 hours after emergency department arrival were similar (PRBC-LyoPlas eleven (7%) of 148 compared with sodium chloride nine (7%) of 137). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in the sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the sodium chloride group (abnormal liver function test). There were no treatment-related deaths.
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Systematic review and meta-analysis of arterial embolization compared with traditional management on outcomes of traumatic massive facial haemorrhage
Stallwood-Hall C, Anderson J, Ebeid A
ANZ journal of surgery. 2022
Abstract
BACKGROUND Maxillofacial trauma accounts for ~10% of trauma presentations to most centres, with massive haemorrhage occurring in 1.2-4.5% of cases. Despite its infrequent presentation, there is significant associated morbidity and mortality. Transcatheter arterial embolization (TAE) is playing an increasingly prominent role in trauma presentations. The aim of this article was to compare outcomes of TAE with more traditional management methods for the treatment of massive facial haemorrhage following maxillofacial trauma. METHODS A database and Google Scholar search was performed, with articles discussing massive facial haemorrhage secondary to maxillofacial trauma and its management included. RESULTS Twenty-seven articles were found that met inclusion criteria, encompassing 384 patients. Statistical testing comparing mortality between TAE and non-TAE groups did not find a significant difference, with a mortality rate of 30.2% in the TAE group and 38.9% in the non-TAE group. Assessment of morbidity directly related to interventions was difficult, as many of the included participants had significant associated injuries which contributed an indeterminate degree to morbidity. There was a 10% rate of adverse events associated with TAE, most commonly puncture site haematomas and soft tissue swelling, with more significant adverse events including cerebrovascular accidents and blindness. CONCLUSION Embolization was correlated with increased rates of haemorrhage control when compared with other interventions. Overall, despite no significant impact on mortality, embolization is recommended in the management of massive haemorrhage following maxillofacial trauma due to improved success rates at haemorrhage control and a low rate of significant adverse events.
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Recommendations for Improving Stop the Bleed: A Systematic Review
Nichols R, Horstman J
Military medicine. 2022
Abstract
INTRODUCTION In response to mass casualty events, The Hartford Consensus brought together subject matter experts across multiple disciplines in health care and public safety to create guidelines and publications intended to improve survivability in active shooter events. Among the recommendations was the earlier recognition and treatment application of life-threatening hemorrhage control. These recommendations culminated in efforts to create the Stop the Bleed Campaign, which aims to empower the layperson to render aid in a life-threatening bleeding emergency. As of February 2020, the program has held over 86,000 courses, trained over 1.4 million attendees, and over 77,000 instructors since its inception. In addition to spreading within the United States, American College of Surgeons (ACS) Stop the Bleed (StB) classes have been held in 118 different countries. This systematic narrative review aims to answer the following research question: What does the ACS StB Initiative do well, and where can it improve? MATERIALS AND METHODS The following search terms were utilized: "Stop the Bleed," "American College of Surgeons," "bleeding control," "first-aid," tourniquet, "wound pack," "direct pressure" hemorrhage, and bystander. The inclusion criteria were that the article needed to speak to the program or some aspect of bystander first aid, the article needed to be in a civilian setting, the article needed to be more than a case study or overview, and the first aid tools needed to be in the StB curriculum. 4 databases were searched, which produced 138 articles for screening. One hundred four full-text articles were able to be retrieved, and 56 articles were determined to meet the inclusion criteria once the full text was reviewed. RESULTS Fifty-six articles were included in the final review and were placed into the following categories: Needs Within the Community, Confidence and Knowledge, Training Modalities, Barriers and Gaps in Training, Instructor Selection, Skill Retention, and Patient Outcomes. The articles were then organized into each outcome for synthesis and reporting of the results. The program overwhelmingly improves short-term confidence, but gaps in skill retention, data collection on patient outcomes, and settings that would benefit were identified. CONCLUSION StB is an effective tool in building confidence in laypersons, which is its biggest strength. A review of the literature shows several areas where the curriculum and materials could be better developed. Research can also be further refined to better quantify the program's impact.
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To Analyze the Role of Intravenous Tranexamic Acid in Hip Fracture surgeries in Orthopedic Trauma
Sahni G, Sood M, Girdhar D, Sahni P, Jain AK, Kumar S
International journal of applied & basic medical research. 2021;11(3):139-142
Abstract
INTRODUCTION Hip fractures in orthopedic trauma cases are increasing. Majority of such patients undergoing surgery require blood transfusion of one or more units. Intravenous (I. V.) Tranexamic acid (TXA) may decrease loss of blood, decrease need of blood transfusion, and improve postoperative hemoglobin (Hb) along with lesser adverse effects. Risk of thromboembolic phenomena remains a concern. A study was done to analyze the role of I. V. TXA in hip fracture surgeries in trauma cases. MATERIALS AND METHODS Sixty patients were included in the study; in two groups (37 males and 23 females), Group A in which two doses of I. V. TXA 15 mg/kg were given and Group B in which two doses of I. V. placebo were given. RESULTS Total number of randomized hip arthroplasty cases was 22 (11 in Group A and 11 in Group B) whereas randomized osteosynthesis cases were 38 (19 in Group A and 19 in Group B). Mean preoperative Hb value in Group A was 10.8 gm% and in Group B was 10.7 gm% (P > 0.005. Mean postoperative Hb value in Group A was Hb 9.8 gm% and in Group B 9.5 gm% (difference of 3.061%). Mean duration of surgery in Group A was 64.2 min and in Group B was 66.3 min. Mean total blood loss (intraoperative and postoperative) in Group A was 384.6 ml and in Group B was 448.7 ml (14.29% less in Group A). A total of 14 patients in Group A (17 red blood cells [RBCs] units) and 17 patients (21 RBC units) in Group B required RBC transfusion. No major vascular event, severe bacterial infections, symptomatic deep vein thrombosis, pulmonary embolism, limb ischemia, acute coronary syndrome, or immediate postoperative mortality was noted in either group. CONCLUSION I. V. TXA has the potential to decrease risk of blood transfusion, decrease total blood loss, and to maintain a higher postoperative Hb value with no significant adverse reactions. As the number of cases of hip fractures continues to increase along with increase in age, so the use of TXA in such cases may improve clinical outcomes, lessen number of inpatient days and hence decrease overall cost.
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The Windlass Tourniquet: Is It Taking the Wind Out of the "Stop the Bleed" Sails?
Schlanser VL, Tatebe LC, Karalius VP, Liesen E, Pekarek S, Impens A, Ivkovic K, Bajani F, Khalifa A, Dennis AJ
The Journal of surgical research. 2021;271:91-97
Abstract
BACKGROUND Civilians are often first-line responders in hemorrhage control; however, windlass tourniquets are not intuitive. Untrained users reading enclosed instructions failed in 38.2% of tourniquet applications. This prospective follow-up study replicated testing following Stop the Bleed (STB) training. MATERIALS AND METHODS One and six months following STB, first-year medical students were randomly assigned a windlass tourniquet with enclosed instructions. Each was given one minute to read instructions and two minutes to apply the windlass tourniquet on the TraumaFX HEMO trainer. Demographics, time to read instructions and stop bleeding, blood loss, and simulation success were analyzed. RESULTS 100 students received STB training. 31 and 34 students completed tourniquet testing at one month and six months, respectively. At both intervals, 38% of students were unable to control hemorrhage (P = 0.97). When compared to the pilot study without STB training (median 48 sec, IQR 33-60 sec), the time taken to read the instructions was shorter one month following STB (P <0.001), but there was no difference at 6 months (P = 0.1). Incorrect placement was noted for 19.4% and 23.5% of attempts at 1 and 6 months. Male participants were more successful in effective placement at one month (93.3% versus 31.3%, P = 0.004) and at six months (77.8% versus 43.8%, p = 0.04). CONCLUSIONS Skills decay for tourniquet application was observed between 1 and 6 months following STB. Instruction review and STB produced the same hemorrhage control rates as reading enclosed instructions without prior training. Training efforts must continue; but an intuitive tourniquet relying less on mechanical advantage is needed.
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The risks associated with tourniquet use in lower limb trauma surgery: a systematic review and meta-analysis
Farhan-Alanie MM, Dhaif F, Trompeter A, Underwood M, Yeung J, Parsons N, Metcalfe A, Wall PDH
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2021
Abstract
PURPOSE Tourniquet use in lower limb fracture surgery may reduce intra-operative bleeding, improve surgical field of view and reduce length of procedure. However, tourniquets may result in pain and the production of harmful metabolites cause complications or affect functional outcomes. This systematic review aimed to compare outcomes following lower limb fracture surgery performed with or without tourniquet. METHODS We searched databases for RCTs comparing lower limb fracture surgery performed with versus without tourniquet reporting on outcomes pain, physical function, health-related quality of life, complications, cognitive function, blood loss, length of stay, length of procedure, swelling, time to union, surgical field of view, volume of anaesthetic agent, biochemical markers of inflammation and injury, and electrolyte and acid-base balance. Random-effects meta-analysis was performed. PROSPERO ID CRD42020209310. RESULTS Six RCTs enabled inclusion of 552 procedures. Pooled analysis demonstrated that tourniquet use reduced length of procedure by 6 minutes (95% CI -10.12 to -1.87; p < 0.010). We were unable to exclude increased harms from tourniquet use. Pooled analysis showed post-operative pain score was higher in tourniquet group by 12.88 on 100-point scale (95% CI -1.25-27.02; p = 0.070). Risk differences for wound infection, deep venous thrombosis and re-operation were 0.06 (95% CI -0.00-0.12; p = 0.070), 0.05 (95% CI -0.02-0.11; p = 0.150) and 0.03 (95% CI -0.03-0.09; p = 0.340). CONCLUSION Tourniquet use was associated with a reduced length of procedure. It is possible that tourniquets also increase incidence of important complications, but the data are too sparse to draw firm conclusions. Methodological weaknesses of the included RCTs prevent any solid conclusions being drawn for outcomes investigated. Further studies are required to address these limitations.
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Early Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Jiao X, Li M, Li L, Hu X, Guo X, Lu Y
Frontiers in neurology. 2021;12:721125
Abstract
Objective: Intracranial hemorrhage (ICH) is a common complication of traumatic brain, in which tranexamic acid has been recommended as an additional therapy to prevent a second bleeding. However, the effect of early administration of tranexamic acid for ICH patients remains controversial. Methods: A systematic search was performed in Cochrane Library, Medline, Embase, and Web of Science. Poor outcome refers to significant hemorrhage growth, new intracranial hemorrhage, new focal cerebral ischaemic lesions, the need for neurosurgery, or death. Study heterogeneity and publication bias were estimated. Results: Seven randomized controlled trials involving 3,192 participants were included in our meta-analysis. Tranexamic acid administration in ICH patients was associated with better outcomes of hematoma expansion (odd ratios [OR] 0.79; 95% confidence interval (CI) CI, 0.67-0.93; I (2) = 0%; P = 0.006) and growth of hemorrhagic lesions (weighted mean difference [WMD], -1.97 ml; 95% CI, -2.94 to -1.00; I (2) = 14%; P < 0.001) than the placebo. No difference was found between the mortality, poor outcome, neurosurgical intervention, new bleeding, and the duration of hospital stay. Moreover, no publication bias was found. Conclusion: Our analysis reveals that the early treatment with tranexamic acid can significantly reduce the incidence of hematoma expansion and the volume of hemorrhagic lesion, but does not exert considerable effects on mortality, poor outcome, neurosurgery, rebleeding, and the duration of stay.
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10.
Accuracy of risk tools to predict critical bleeding in major trauma: a systematic review with meta-analysis
Gianola S, Castellini G, Biffi A, Porcu G, Napoletano A, Coclite D, D'Angelo D, Fauci AJ, Iacorossi L, Latina R, et al
The journal of trauma and acute care surgery. 2021
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Editor's Choice
Abstract
BACKGROUND Early detection of critical bleeding by accurate tools can help ensure rapid delivery of blood products to improve outcomes in major trauma patients. We conducted a systematic review to evaluate the accuracy of risk tools to predict critical bleeding in patients with major trauma. METHODS PubMed, Embase and CENTRAL were searched up to February 2021 for studies investigating risk tools to predict critical bleeding for major trauma people in pre-hospital and emergency department. We followed the PRISMA-DTA guidelines. Two independent authors included studies, extracted data, appraised the quality using the Quality Assessment of Diagnostic Accuracy Studies-2 and assessed the certainty of evidence using thee Grading of Recommendations Assessment, Development and Evaluation methodology. Sensitivity, specificity and the Receiver Operating Characteristics curve for all selected triage tools. RESULTS Eighty-nine observational studies for adults and 12 observational studies for children met our inclusion criteria. In adults, we found 23 externally validated and 28 un-validated tools; in children, 3 externally validated tools and 5 un-validated. In the externally validated tools, we identified those including clinical, laboratory and ultrasound assessments. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Pediatric Age-adjusted (SIPA) with a moderate Certainty of Evidence. We found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components. CONCLUSIONS Clinicians should consider risk tools to predict critical bleeding in a time-sensitive setting like major life threatening trauma. The Shock index and SIPA are easy and handy tools to predict critical bleeding in the pre-hospital setting. In the emergency department, however, many other tools can be utilized which include laboratory and ultrasound assessments, depending on staff experience and resources. LEVEL OF EVIDENCE Systematic review, diagnostic Level III.
PICO Summary
Population
Adults and children with major trauma (101 studies).
Intervention
Systematic review to identify the most accurate risk tools to predict critical bleeding.
Comparison
Outcome
Twenty-three externally validated and 28 un-validated tools were found for adults, and 3 externally validated tools and 5 un-validated, for children. Among tools including only a clinical assessment, the Shock Index showed high sensitivity and specificity with the Certainty of Evidence ranging from very low to moderate in adults, as well as Shock Index Paediatric Age-adjusted with a moderate Certainty of Evidence. It was found that tools using clinical, laboratory and ultrasound assessments were overall more accurate than those tools without all three components.