Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial
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- 作者：Ian Roberts (1)
David Prieto-Merino (1)
Daniela Manno (1)
1. Clinical Trials Unit ; London School of Hygiene & Tropical Medicine ; Keppel Street ; London ; WC1E 7HT ; UK - 刊名：Critical Care
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：18
- 期：6
- 全文大小：483 KB
- 参考文献：1. The CRASH-2 Collaborators: class="a-plus-plus">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. / Lancet 2010, class="a-plus-plus">376:23鈥?2.
2. The CRASH-2 collaborators: class="a-plus-plus">The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. / Lancet 2011, class="a-plus-plus">377:1096鈥?101.
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- 出版者：BioMed Central
- ISSN：1364-8535
文摘
Introduction To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days. Methods Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov NCT00375258. Results The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3聽hours of their injury (HR 鈮?聽hours = 0.78, 0.68 to 0.90; HR >3聽hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3聽hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3聽hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise. Conclusions Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.