The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trialThe CRASH-2 collaborators* SummaryBackground 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.Methods The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, signifi cant 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 eff ect 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 eff ect 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) signifi cantly reduced the risk of death due to bleeding (198 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 eff ective and could be harmful.Funding UK NIHR Health Technology Assessment programme, Pfi zer, BUPA Foundation, and J P Moulton Charitable Foundation. IntroductionThe CRASH-2 trial showed that administration of tranexamic acid to adult trauma patients with, or at risk of, signifi cant haemorrhage, within 8 h of injury, signi fi cantly reduces all-cause mortality (relative risk [RR] 0·91, 95% CI 0·85-0·97; p=0·0035) with no apparent increase in vascular occlusive events.1 As a consequence of this trial, tranexamic acid has been incorporated into trauma treatment protocols worldwide.Results from the CRASH-2 trial raise some important questions. The trial was motivated by the evidence that tranexamic acid reduces bleeding in patients undergoing elective surgery, and the hypothesised mechanism was inhi...

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2015, Issue 2 http://www.thecochranelibrary.com 0induced coagulopathy in adult trauma patients with bleeding Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding (Review)

It is feasible to use TEM in a deployed military setting. We have shown that rotational thromboelastometry significantly detects more abnormalities in the coagulation status than the standard laboratory tests (prothrombin time, and activated partial thromboplastin time).

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Damage control resuscitation (DCR) is a strategy for resuscitating patients from hemorrhagic shock to rapidly restore homeostasis. Efforts are focused on blood product transfusion with whole blood or component therapy closely approximating whole blood, limited use of crystalloid to avoid dilutional coagulopathy, hypotensive resuscitation until bleeding control is achieved, empiric use of tranexamic acid, prevention of acidosis and hypothermia, and rapid definitive surgical control of bleeding. Patients receiving uncrossmatched Type O blood in the emergency department and later receiving cumulative transfusions of 10 or more red blood cell units in the initial 24-hour post-injury (massive transfusion) are widely recognized as being at increased risk of morbidity and mortality due to exsanguination. Ideally, these patients should be rapidly identified, however anticipating transfusion needs is challenging. Useful indicators of massive transfusion reviewed in this guideline include: systolic blood pressure <110 mmHg, heart rate > 105 bpm, hematocrit <32%, pH < 7.25, injury pattern (above-the-knee traumatic amputation especially if pelvic injury is present, multi-amputation, clinically obvious penetrating injury to chest or abdomen), >2 regions positive on Focused Assessment with Sonography for Trauma (FAST) scan, lactate concentration on admission >2.5, admission international normalized ratio ≥1.2-1.4, near infrared spectroscopy-derived StO2 < 75% (in practice, rarely available), BD > 6 meq/L. Unique aspects of out-of-hospital DCR (point of injury, en-route, and remote DCR) and in-hospital (Medical Treatment Facilities: Role 2b/Forward surgical teams - role 3/ combat support hospitals) are reviewed in this guideline, along with pediatric considerations.

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The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR). A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes. Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network's opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation.The THOR Network's consensus statement is, "In a casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components. As a part of this HR, the initial systolic blood pressure target should be 100 mm Hg. In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock".