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| 題 名 | 發炎,凝血與血管內皮細胞--嚴重敗血症的抗血栓治療=Inflammation, Coagulopathy and Endothelium--Novel Anticoaglant Therapy in Sepsis |
|---|---|
| 作 者 | 尹彙文; | 書刊名 | 中華民國重症醫學雜誌 |
| 卷 期 | 5:1 2003.01[民92.01] |
| 頁 次 | 頁77-83 |
| 分類號 | 415.6 |
| 關鍵詞 | 敗血症; 發炎反應; 凝血異常; Sepsis; Inflammation; Coagulopathy; |
| 語 文 | 中文(Chinese) |
| 中文摘要 | 敗血症,是一種全身性發炎反應症候群,是宿主對外來感染菌種或某種壓力因素的宿主防禦反應,因此這種自衛機制必須剛好平衡,防衛過當(抗發炎反應太強)造成免疫功能低下或是防衛不足(持續進行發炎反應)造成多重器官衰竭,對身體的生理功能均是額外不必要的傷害,每年敗血症在美國的發生案例約75萬人,至少造成百分之30的死亡發生;而在加護病房的敗血症死亡率約在百分之30至50之間,佔美國死亡主因的第11位。因為敗血症具有如此高的發生率與死亡率,如何治療一直是醫學界相當棘手的問題。 針對敗血症的機轉所進行的研究,在過去數十年間有許多文獻被發表,在90年代,敗血症的研究把焦點放在針對促發炎介質及抗發炎介質二者間的失衡給予拮抗劑的研發,想從中找根本治療敗血症的神奇子彈,而且在過去十年,製藥業在研究治療敗血症的臨床試驗上,卻無明顯的療效被發現。直到最近,對於敗血症的致病機轉有了更清楚的瞭解後,對於治療的突破,開始顯現了曙光。 人類活性蛋白C具有促進血栓溶解及抗發炎的功效,可以幫助維持血流通暢以及防止多重器官衰竭的發生:在許多研究發現,若是敗血症患者血中活性蛋白C的濃度降低則死亡率明顯增加。而活性蛋白C是利用基因工程技術來產生的人體蛋白-活性蛋白C,在第一、二期的敗血症臨床研究顯示,活性蛋白C可以有效降低血中發炎生物素的活性,抑制血栓及發炎反應的產生。在第三期共有11個國家參予的國際治療重度敗血症的臨床研究,共有1690位敗血症合併急性器官功能障礙的患者,隨機接受新藥活性蛋白C或安慰劑治療,結果發現活性蛋白C(美國FDA核准用)在治療具高死亡風險(APACH分數大於25)的嚴重敗血症患者,確實有顯著的療效。由失衡的凝血反應在嚴重敗血症病程中的角色來看,活性蛋白C的確是一個具臨床價值的治療藥物,許多活性蛋白C的優勢,例如在調控微血管凝集病變中所具有的獨特角色,支持我們繼續去發展與活性蛋白C相關的治療策略,來打斷整個發炎反應和凝集反應形成的疾病過程。我們期待在不久的將來,更多的實證研究支持此一治療策略,更進一步的改善敗血症重症病人的存活率。 |
| 英文摘要 | Therapeutic interventions in sepsis during the past 20 years have focused on attenuating the cascades associated with inflammation. Treatments such as antiendotoxin, interleukin-1 receptor antagonist (IL-Jra), tumor necrosis factor antibodies, and cyclooxygenase have failed to significantly reduce mortality in patients with severe sepsis. Severe sepsis continues to have high incidence of morbidity and mortality, with many healthcare workers expressing serious concerns about the validity of current randomized controlled trial methodology in severe sepsis and associated organ dysfunction. Although potential explanations for the failure of these trials are many, a possible explanation is that they have addressed a single pathogenic process rather than the multiple, interlocking events associated with this disorder. Innate immunity, inflammation and coagulation are tightly linked. As a result of evidences among these associations, there has been a recent shift toward targeting both the inflammatory and hemostatic abnormalities of severe sepsis with phase III trials of antithrombin, tissue factor pathway inhibitor, and protein C. Deficiency in protein C has been proved in most adult and pediatric patients with severe sepsis and is associated with an increased risk of mortality. After its activation by thrombomodulin-bound thrombin, activated protein C inhibits thrombosis, promotes fibrinolysis, downregulates inflammation, and inhibits endothelial cell apoptosis. The results of the PROWESS trial provide the first major advance in the treatment of severe sepsis. The PROWESS trial demonstrated that treatment with activated protein C produced a 6.1% absolute reduction in mortality and 19.4% relative reduction in the adjusted risk of death from all-cause within 28 days in patients with severe sepsis. Because of the first approved agent in a new category of antiseptic interventions, we clinicians need to be familiar with this new finding, indications and contraindications. |
本系統中英文摘要資訊取自各篇刊載內容。