- 期刊
皮質類固醇與活化蛋白質C在敗血症之臨床應用
The Clinical Applications of Corticosteroids and Recombinant Human Activated Protein C in Patients with Severe Sepsis
摘要
根據行政院衛生署統計資料顯示，近年來，國人主要死亡原因中，死於敗血症的人數逐年增加，排名也從第14位（2000年）上升至第12位（2006年），敗血症也一直是加護病房中主要的死亡原因。如何有效增進敗血症的治療效果及改善死亡率，也一直是目前積極研究的目標。其中皮質類固醇和活化蛋白質C對於敗血症的治療已有許多正面的結果， 整體而言，皮質類固醇(cortisol)，主要是由腎上腺束狀帶細胞(Zona fasciculata)和網狀帶細胞(Zona Reticularis)所分泌，在罹患敗血症的病人，常會因爲腎上腺功能低下，體內無法產生足夠的皮質類固醇對抗外來刺激，可能會加速病程之惡化，導致預後不佳。根據2008 年Surviving Sepsis Campaign的建議，對兒茶酚胺(catecholamine)有阻抗性的小孩、疑似或證實是腎上腺功能低下的病人使用皮質類固醇，可以有效改善敗血症病人預後。而活化蛋白質C，可以抑制單核球及內皮細胞釋放組織因子；抑制嗜中性白血球沾附於受損的內皮細胞；減少活化凝血因子VⅢa及Va，減少血栓凝集；抑制PAI-1，促使血栓溶解，能有效減少血栓所引起的多重器官血液灌注缺乏。因此，藉由相關研究文獻，我們針對這些藥物的臨床使用及其治療機轉加以討論及回顧。
並列摘要
Although sepsis is one of the most common causes of death on a global basis and is also the main leading cause of death in intensive care units, the management sometimes remains challenging, thereby portending a significant barrier of prognosis. How to improve the therapeutic efficacy and mortality in patients with sepsis is of paramount importance and particular emphasis should be given to insights derived from the current treatment protocols. Notably, the therapeutic outcomes of hydrocortisone and recombinant human activated protein C in patients with severe sepsis and septic shock are promising. Since cortisol has a powerful anti-inflammatory role by suppressing innate and adaptive immune systems, recommendation of hydrocortisone therapy is only reserved for adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor institution or in pediatric septic shock patients with catecholamine resistance and suspected or proven adrenal insufficiency. Recombinant human activated protein C exerts an antithrombotic effect by inactivating factors Va, VⅢa, decreasing the synthesis of plasminogen-activator inhibitor 1, inhibiting tissue factors released from monocytes and endothelial cell, and reducing the rolling of neutrophils on injured endothelium in order to limit the generation of thrombin and prevent further coagulation cascade. Adult patients with sepsis induced organ dysfunction associated with high risk of death, APACHE Ⅱ≧25 or multiple organ failure are suggested to receive recombinant human activated protein C. The aim of this article is to address the clinical applications and review the mechanistic basis of hydrocortisone and recombinant human activated protein C therapy.