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
Authors:
Trenkler Štefan 1; Laincz Anton 2; Valky Jozef 3; Yaghi Ajtham 4; Svoboda Petr 5
Authors‘ workplace:
Ďalší účastníci sú uvedení na konci článku.
**; Klinika anestéziológie a intenzívnej medicíny, Univerzita P. J. Šafárika a Univerzitná nemocnica L. Pasteura Košice, Slovensko
1; Oddelenie anestéziológie a intenzívnej medicíny, Nemocnica Poprad, a. s., Slovensko
2; Oddelenie anestéziológie a intenzívnej medicíny, Fakultná nemocnica s Poliklinikou F. D. Roosevelta Banská Bystrica
3; Klinika anestéziológie a intenzívnej medicíny, Univerzitná nemocnica Bratislava, Nemocnica Ružinov
4; Úrazová nemocnice v Brně
5
Published in:
Anest. intenziv. Med., 22, 2011, č. 2, s. 103-114
Category:
Intensive Care Medicine - Original Paper
(za spolupracovníky CRASH-2 studie**)
Overview
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 blinded 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.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919.
Findings:
Total 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 (1,463 [14·5%] in the tranexamic acid group vs 1,613 [16·0%] in the 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 5.74 [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.
Keywords:
tranexamic acid – trauma – bleeding – RCT – CRASH-2
Sources
1. Peden, M., McGee, K., Sharma, G. The injury chart book: a graphical overview of the global burden of njuries. Geneva: World Health Organization, 2002.
2. Gosselin, R. A., Spiegel, D. A., Coughlin, R., Zirkled, L. G. Injuries: the neglected burden in developing countries. Bull World Health Organ., 2009, 87, p. 246.
3. Sauaia, A., Moore, F. A., Moore, E. E. et al. Epidemiology of trauma deaths: a reassessment. J. Trauma, 1995, 38, p. 185–93.
4. Lawson, J. H., Murphy, M. P. Challenges for providing effective hemostasis in surgery and trauma. Sem. Hematol., 2004, 41, p. 55–64.
5. Henry, D. A., Carless, P. A., Moxey, A. J. et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood ransfusion. Cochrane Database Syst. Rev., 2007, 4, p. CD001886.
6. Okamoto, S., Hijikata-Okunomiya, A., Wanaka, K., Okada, Y., Okamoto, U. Enzyme controlling medicines: introduction. Semin. Thromb. Hemost., 1997, 23, p. 493–501.
7. Coats, T., Roberts, I., Shakur, H. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst. Rev., 2004, 4, p. CD004896.
8. Baigent, C., Peto, R., Gray, R., Parish, S., Collins, R. Large-scale randomized evidence: trials and meta-analyses of trials. In Warrell, D. A., Cox, T. M., Firth, J. D., eds. Oxford Textbook of Medicine (5th edn). Oxford: Oxford University Press, 2010, p. 31–45.
9. Perel, P., Edwards, P., Shakur, H., Roberts, I. Use of the Oxford Handicap Scale at hospital discharge to predict Glasgow Outcome Scale at 6 months in patients with traumatic brain injury. BMC Med. Res. Methodol., 2008, 8, p. 72.
10. Duley, L., Antman, K., Arena, J. et al. Specific barriers to the conduct of randomized trials. Clin. Trials, 2008, 5, p. 40–48.
11. Sterne, J., White, I., Carlin, J. et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ, 2009, 338, p. b2393.
12. Rogers, A., MacMahon, S. Systematic underestimation of treatment effects as a result of diagnostic test naccuracy: implications for the interpretation and design of thromboprophylaxis trials. Thromb. Haemost., 1995, 73, p. 167–171.
13. Brohi, K., Cohen, M. J., Ganter, M. T. et al. Acute coagulopathy of trauma: hypo-perfusion induces systemic anticoagulation and hyper-fibrinolysis. J. Trauma, 2008, 64, p. 1211–1217.
14. Ekbäck, G., Axelsson, K., Ryttberg, L. et al. Tranexamic acid reduces blood loss in total hip replacement surgery. Anesth. Analg., 2000, 91, p. 1124–1130.
15. Kauvar, D. S., Lefering, R., Wade, C. E. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J. Trauma, 2006, 60, p. S3–11.
16. Mock, C. N., Jurkovich, G. J., Nii-Amon-Kotei, D., Arreola--Risa, C., Maier, R. V. Trauma mortality patterns in three nations at different economic levels: implications for global trauma system development. J. Trauma, 1998, 44, p. 804–812.
17. Wyatt, J., Beard, D., Gray, A., Busuttil, A., Robertson, C. The time of death after trauma. BMJ, 1995, 310, p. 1502.
18. Fiechtner, B. K., Nuttall, G. A., Johnson, M. E. et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth. Analg., 2001, 92, p. 1131–1136.
19. Horrow, J. C., Van Riper, D. F., Strong, M. D., Grunewald, K. E., Parmet, J. L. The dose-response relationship of tranexamic acid. Anesthesiology, 1995, 82, p. 383–392.
20. MRC CRASH Trial Collaborators Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ, 2008, 12, p. 12.
21. Maas, A. I., Steyerberg, E. W., Butcher, I. et al. Prognostic value of computerized tomography scan characteristics in traumatic brain injury: results from the IMPACT study. J. Neurotrauma, 2007, 24, p. 303–314.
22. Perel, P., Roberts, I., Bouamra, O., Woodford, M., Mooney, J., Lecky, F. Intracranial bleeding in patients with traumatic brain injury: a prognostic study. BMC Emerg. Med., 2009, 9, p. 15.
23. Hogan, M. C., Foreman, K. J., Naghavi, M. et al. Maternal mortality for 181 countries, 1980–2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet, 2010, 375, p. 1609–1623.
24. Ferrer, P., Roberts, I., Sydenham, E., Blackhall, K., Shakur, H. Anti-fibrinolytic agents in postpartum haemorrhage: a systematic review. BMC Pregnancy Childbirth, 2009, 9, p. 29.
25. Shakur, H., Elbourne, D., Gülmezoglu, M. et al. The WOMAN Trial (World Maternal Antifibrinolytic Trial): tranexamic acid for the treatment of postpartum haemorrhage: an international randomised, double blind placebo controlled trial. Trials, 2010, 11, p. 40.
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Anaesthesiology, Resuscitation and Inten Intensive Care MedicineArticle was published in
Anaesthesiology and Intensive Care Medicine
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