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Abstract
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Traumatic brain injury (TBI) is among the most dreaded and tragic of diagnoses. At least one clinical trial has shown that despite the most advanced care available, mortality from TBI, either in isolation or with concomitant polytrauma, can exceed 50%.1 Every physician who has cared for patients with TBI has felt the frustration that stems from being unable to alter the fatal course of traumatic brain haemorrhage in a previously healthy person.
Over the past several decades, patients with TBI, their families, and their health-care providers have hoped for improved approaches to treating this condition. Indeed, governments have devoted considerable resources to developing improved management strategies for TBI. What have we learned? Despite compelling physiological logic and promising preclinical data, attempts to treat patients with TBI with such diverse approaches as corticosteroids,2 progesterone,3 and brain cooling4 have been ineffective or worse. Interventions designed to target specific injury mechanisms such as increased permeability of the blood–brain barrier through bradykinin receptor inhibition (anatibant5) are promising but require further study.6 The hard truths of TBI care learned from war and everyday TBI are quite simple and obvious: control bleeding, and avoid hypotension7 and hypoxia,8 or the patient will die.
This study represents an enormous effort in studying a difficult clinical problem. Considering the results of CRASH-3 with those of CRASH-212 (20 211 patients with trauma) and WOMAN13 (20 060 patients with peripartum haemorrhage), more than 53 000 patients have been randomly assigned in the study of tranexamic acid and the drug's effects on patients with bleeding. The results of each study independently and together are clear: tranexamic acid reduces risk of death due to bleeding, regardless of the cause. Furthermore, tranexamic acid must be given early—within 3 h of bleeding onset—to be effective. These data suggest a fundamental truth regarding the pathophysiology of life-threatening haemorrhage—namely, that early activation of the fibrinolytic protease cascade is intimately linked to poor outcomes in patients with bleeding, perhaps because of various mechanisms,15 including worsened bleeding due to clot breakdown, activation of inflammatory pathways, and increased endothelial permeability leading to tissue, especially brain, oedema. Tranexamic acid offers a means to mitigate this maladaptive response to injury...
Language: en |