Tim Coats

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

BACKGROUND Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other AL analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919. RESULTS 10096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10060 and 10067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [160%] placebo group; relative risk 0.91, 95% CI 085-097; p = 00035). The risk of death due to bleeding was significantly reduced (489 [49%] vs 574 [5-7%]; relative risk 0-85, 95% CI 0.76-0.96; p = 0-0077). CONCLUSION Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.BACKGROUND Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. FINDINGS 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). INTERPRETATION Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. FUNDING UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Acute traumatic coagulopathy

BACKGROUND Traumatic coagulopathy is thought to be caused primarily by fluid administration and hypothermia. METHODS A retrospective study was performed to determine whether coagulopathy resulting from the injury itself is a clinically important entity in severely injured patients. RESULTS One thousand eight hundred sixty-seven consecutive trauma patients were reviewed, of whom 1,088 had full data sets. Median Injury Severity Score was 20, and 57.7% had an Injury Severity Score > 15; 24.4% of patients had a significant coagulopathy. Patients with an acute coagulopathy had significantly higher mortality (46.0% vs. 10.9%; chi2, p < 0.001). The incidence of coagulopathy increased with severity of injury, but was not related to the volume of intravenous fluid administered (r2 = 0.25, p < 0.001). CONCLUSION There is a common and clinically important acute traumatic coagulopathy that is not related to fluid administration. This is a marker of injury severity and is related to mortality. A coagulation screen is an important early test in severely injured patients.

Management of bleeding and coagulopathy following major trauma: an updated European guideline

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsA comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.http://ccforum.com/content/17/4/442

Trial of early, goal-directed resuscitation for septic shock.

BACKGROUND Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. METHODS We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. RESULTS We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. CONCLUSIONS In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial.

Background The aim of the CRASH-2 trial was to assess the eff ects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with signifi cant haemorrhage. Tranexamic acid signifi cantly reduced all-cause mortality. Because tranexamic acid is thought to exert its eff ect through inhibition of fi brinolysis, we undertook exploratory analyses of its eff ect on death due to bleeding.BACKGROUND The aim of the CRASH-2 trial was to assess the effects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage. Tranexamic acid significantly reduced all-cause mortality. Because tranexamic acid is thought to exert its effect through inhibition of fibrinolysis, we undertook exploratory analyses of its effect on death due to bleeding. METHODS The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20,211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the effect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919. FINDINGS 10,096 patients were allocated to tranexamic acid and 10,115 to placebo, of whom 10,060 and 10,067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the effect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0.0001). Early treatment (≤1 h from injury) significantly reduced the risk of death due to bleeding (198/3747 [5.3%] events in tranexamic acid group vs 286/3704 [7.7%] in placebo group; relative risk [RR] 0.68, 95% CI 0.57-0.82; p<0.0001). Treatment given between 1 and 3 h also reduced the risk of death due to bleeding (147/3037 [4.8%] vs 184/2996 [6.1%]; RR 0.79, 0.64-0.97; p=0.03). Treatment given after 3 h seemed to increase the risk of death due to bleeding (144/3272 [4.4%] vs 103/3362 [3.1%]; RR 1.44, 1.12-1.84; p=0.004). We recorded no evidence that the effect of tranexamic acid on death due to bleeding varied by systolic blood pressure, Glasgow coma score, or type of injury. INTERPRETATION Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less effective and could be harmful. FUNDING UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Management of bleeding following major trauma: an updated European guideline

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsThis guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

The European guideline on management of major bleeding and coagulopathy following trauma: Fourth edition

BackgroundSevere trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution.MethodsThe pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013.ResultsThe guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome.ConclusionsA multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

The Utstein template for uniform reporting of data following major trauma: A joint revision by SCANTEM, TARN, DGU-TR and RITG

BackgroundIn 1999, an Utstein Template for Uniform Reporting of Data following Major Trauma was published. Few papers have since been published based on that template, reflecting a lack of international consensus on its feasibility and use. The aim of the present revision was to further develop the Utstein Template, particularly with a major reduction in the number of core data variables and the addition of more precise definitions of data variables. In addition, we wanted to define a set of inclusion and exclusion criteria that will facilitate uniform comparison of trauma cases.MethodsOver a ten-month period, selected experts from major European trauma registries and organisations carried out an Utstein consensus process based on a modified nominal group technique.ResultsThe expert panel concluded that a New Injury Severity Score > 15 should be used as a single inclusion criterion, and five exclusion criteria were also selected. Thirty-five precisely defined core data variables were agreed upon, with further division into core data for Predictive models, System Characteristic Descriptors and for Process Mapping.ConclusionThrough a structured consensus process, the Utstein Template for Uniform Reporting of Data following Major Trauma has been revised. This revision will enhance national and international comparisons of trauma systems, and will form the basis for improved prediction models in trauma care.

Prehospital resuscitative thoracotomy for cardiac arrest after penetrating trauma: rationale and case series.

OBJECTIVE The purpose of this study is to present the rationale for an algorithm that describes the place of resuscitative thoracotomy in the prehospital management of a patient with penetrating chest injury, and to review a 6-year experience using this algorithm. METHODS This study was a retrospective review of all cases where a prehospital thoracotomy was performed by the medical teams of the London Helicopter Emergency Medical Service. RESULTS Thirty-nine prehospital thoracotomies were performed. Four (10%) patients survived, one with long-term disability. Factors associated with survival were stab wound, single cardiac wound, cardiac tamponade, and loss of pulse in the presence of an experienced prehospital doctor. CONCLUSION Current evidence suggests that patients who suffer a cardiac arrest more than 10 minutes away from emergency room thoracotomy are very unlikely to survive. Prehospital thoracotomy is associated with a small number of survivors. This intervention should be considered if there is an appropriately experienced, trained, and equipped doctor present, who is acting within a trauma system with ongoing training and quality assurance.

Key issues in advanced bleeding care in trauma.

ABSTRACT The incidence of hemostatic abnormalities in the early hours after traumatic incident is high and represents an independent predictor of mortality. Key factors in the development of traumatic coagulopathy include the severity of injury, hypothermia, acidosis, hemorrhagic shock, hemodilution, clotting factor consumption, and fibrinolysis. Assessment of bleeding includes evaluation of the mechanism of injury, vital signs, biochemistry, detection of external and internal bleeding sources, injuries found upon secondary investigation, and response to treatment. Priority in treating the bleeding trauma patient should be given to prevention of further bleeding, hypothermia, acidosis, coagulopathy, and maintenance of tissue oxygenation, achieved by careful physical handling, damage control surgery, analgesia, maintenance of normothermia, correction of coagulopathy, control of blood pH, and serum calcium. Priority during initial treatment is to restore tissue perfusion and achieve hemostasis in vital functions; other nonvital procedures may generally be delayed. This state-of-the-art review aims to address key issues in acute control of bleeding in the trauma patient.