Baudo F, de Cataldo F
Modulo Trombosi ed Emostasi Ospedale Niguarda Cà Granda, Milano.
Minerva Anestesiol. 2000 Nov;66(11 Suppl 1):3-23.
Sepsis and septic shock are the most frequent cause of mortality in non cardiologic intensive care units. Mortality of the severe form is still elevated in spite of the progress in the antibiotic therapy and in the hemodynamic and respiratory support. The most frequent cause of death is the Multi Organ Dysfunction Syndrome (MODS). The excessive inflammatory reaction and the damage of the microvascular bed secondary to the inflammation and to the disseminated intravascular coagulation (DIC) are important pathogenetic factors. In the sepsis a complex system of cellular activation initiates the release and the interaction of activators and inhibitors of the inflammation (cytokines), the activation of the enzymatic cascade systems (coagulation, fibrinolytic and complement systems) and the synthesis of proteases and anti proteases. The activation of the coagulation system, uncontrolled by the fibrinolytic system with formation of fibrin in the micro vascular bed, has an important role in the MODS. Experimental data and clinical observations suggest a possible therapeutic role of antithrombin III (AT) in sepsis; its plasma concentration is constantly decreased in patients with sepsis or septic shock and the entity of the decrease is correlated with the severity of the clinical picture and the outcome. At has a double function: regulation of the coagulation system and anti inflammatory properties. The anti inflammatory properties depend in part on the binding to the glycosaminoglycans of the endothelial cells and the consequent release of prostacyclin (PGI2). The anti inflammatory effect is independent from the anticoagulant one. The preliminary studies on the clinical use of AT were carried out in small groups of patients with DIC associated with pathologies of different etiology and often in very critical conditions. In general the evaluation criteria were the improvement or the normalization of the laboratory data. The interpretation of the therapeutic effect of AT is difficult because the dysomogeneity of these studies. The effect on mortality is controversial. Recently three prospective, randomized, double blind studies have been published in patients with severe sepsis and septic shock. The results of the single studies are inconclusive but the limited number of patients included in each study may explain the results. A meta-analysis of the data referring to the patients with severe sepsis and septic shock evidenced an odd ratio (OR) of 0.43 with 95% confidential interval of 0.20-0.92 (p = 0.029). The preliminary analysis of the results of a phase III study is unconclusive. Time, dosage and duration of treatment are still open to question. In perspective AT may be used in other clinical conditions associated with activation of the hemostatic system (cardiac surgery, stem cell transplantation, burns) even though the preliminary results must be confirmed by prospective studies. All these data suggest severe sepsis and septic shock as main criteria for treatment.
脓毒症和脓毒性休克是非心脏重症监护病房中最常见的死亡原因。尽管在抗生素治疗、血流动力学和呼吸支持方面取得了进展，但严重形式的死亡率仍然居高不下。最常见的死亡原因是多器官功能障碍综合征（MODS）。过度的炎症反应以及炎症和弥散性血管内凝血（DIC）继发的微血管床损伤是重要的发病因素。在脓毒症中，一个复杂的细胞激活系统启动炎症激活剂和抑制剂（细胞因子）的释放与相互作用、酶级联系统（凝血、纤溶和补体系统）的激活以及蛋白酶和抗蛋白酶的合成。凝血系统的激活不受纤溶系统控制，在微血管床形成纤维蛋白，在MODS中起重要作用。实验数据和临床观察表明抗凝血酶III（AT）在脓毒症中可能具有治疗作用；脓毒症或脓毒性休克患者的血浆浓度持续降低，降低的程度与临床表现的严重程度和预后相关。AT具有双重功能：调节凝血系统和抗炎特性。抗炎特性部分取决于与内皮细胞糖胺聚糖的结合以及随后前列环素（PGI2）的释放。抗炎作用独立于抗凝作用。关于AT临床应用的初步研究是在患有不同病因疾病且通常处于非常危急状况的小部分DIC患者中进行的。一般来说，评估标准是实验室数据的改善或正常化。由于这些研究的异质性，对AT治疗效果的解释很困难。对死亡率的影响存在争议。最近，针对严重脓毒症和脓毒性休克患者发表了三项前瞻性、随机、双盲研究。单项研究的结果尚无定论，但每项研究纳入的患者数量有限可能解释了这些结果。对严重脓毒症和脓毒性休克患者数据的荟萃分析显示，比值比（OR）为0.43，95%置信区间为0.20 - 0.92（p = 0.029）。一项III期研究结果的初步分析尚无定论。治疗的时间、剂量和持续时间仍有待探讨。从长远来看，AT可能用于与止血系统激活相关的其他临床情况（心脏手术、干细胞移植、烧伤），尽管初步结果必须通过前瞻性研究来证实。所有这些数据表明严重脓毒症和脓毒性休克是主要的治疗标准。
