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为何脓毒症抗凝研究经常失败 --- 从 SCARLET 研究开始。

Why anticoagulant studies on sepsis fail frequently --- start with SCARLET.

机构信息

Department of the Intensive Care Unit, The Fourth Medical Center of General Hospital of PLA, 100048, Beijing, China.

Department of the Intensive Care Unit, The Fourth Medical Center of General Hospital of PLA, 100048, Beijing, China.

出版信息

Chin J Traumatol. 2023 Sep;26(5):297-302. doi: 10.1016/j.cjtee.2023.04.006. Epub 2023 May 2.

Abstract

The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.

摘要

Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) 试验存在诸多缺陷,因此不能成为重组血栓调节蛋白(rTM)的终结者。相反,它为进一步的研究提供了充分的证据。基于对 SCARLET 试验失败和几项先前抗凝研究的分析,新的研究最重要的是要把握以下两点:(1)纳入的病例应具有足够的疾病严重程度和弥散性血管内凝血的明确标准;(2)不应将肝素与研究药物联合使用。多项事后分析表明,不联合使用肝素不会增加血栓栓塞的风险。事实上,肝素的联合使用可能会掩盖研究药物的真实疗效。由于脓毒症治疗的复杂性和临床研究的局限性,所有治疗研究的结果都应反复验证,而不是一锤定音。一些与疾病生理学、药理学和临床实践相悖的研究结论可能具有欺骗性,应谨慎对待,而不是简单地接受。另一方面,在“共识”场景中的不同意见往往会被作者很好地讨论,应该高度重视。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d6e/10533541/dbe992ecc4d2/gr1.jpg

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