Waydhas C, Nast-Kolb D, Gippner-Steppert C, Trupka A, Pfundstein C, Schweiberer L, Jochum M
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians-University, Munich, Germany.
J Trauma. 1998 Nov;45(5):931-40. doi: 10.1097/00005373-199811000-00015.
Antithrombin III (AT III) treatment has been shown to reduce disseminated intravascular coagulation and to inhibit thrombin, which plays a central role in the activation of platelets and other inflammatory systems in conditions with severe inflammation. The objective of this study was to evaluate the influence of early and high-dose administration of AT III to patients with severe multiple injuries on the inflammatory response and outcome.
In a placebo-controlled, double-blind study, 40 consecutive patients with Injury Severity Scores of 29 or greater who met the inclusion criteria were randomized to receive either AT III or placebo within 360 minutes after trauma. Twenty patients were administered AT III for a period of 4 days, aiming to achieve AT III concentrations of 140% of normal.
The AT III and placebo groups were comparable with respect to Injury Severity Score, age, incidence of blood pressure less than 80 mm Hg on admission, initial base deficit, and start of the test drug. The patients in the AT III group received a total of about 20,000 IU during the first 4 days. AT III levels of 130 to 140% could be achieved by this regimen, whereas in the control group the AT III concentration averaged about 70%. In the AT III group prothrombin tended to be elevated and prothrombin fragment F1+2 as well as thrombin-AT III complex tended to be lower on the first day. No differences between groups, however, could be observed with respect to partial thromboplastin time, prothrombin time, platelets, plasminogen activator inhibitor I, soluble tumor necrosis factor receptor II, neutrophil elastase, interleukin (IL)-1 receptor antagonist, IL-6, and IL-8. Mortality (15 vs. 5%), incidence of respiratory failure (55 vs. 55%), duration of mechanical ventilation (13 vs. 12 days), and length of stay in the surgical intensive care unit (19 vs. 21 days) were also similar in both treatment groups. The duration of organ failure, however, was shorter in the patients receiving AT III.
The early and high-dose administration of AT III to patients with severe blunt trauma appears not to attenuate the posttraumatic inflammatory response or to significantly improve outcome.
抗凝血酶III（AT III）治疗已被证明可减少弥散性血管内凝血并抑制凝血酶，凝血酶在严重炎症状态下血小板和其他炎症系统的激活中起核心作用。本研究的目的是评估早期大剂量给予AT III对严重多发伤患者炎症反应和预后的影响。
在一项安慰剂对照、双盲研究中，40例连续入选的损伤严重度评分29分及以上且符合纳入标准的患者在创伤后360分钟内随机接受AT III或安慰剂治疗。20例患者接受AT III治疗4天，目标是使AT III浓度达到正常水平的140%。
AT III组和安慰剂组在损伤严重度评分、年龄、入院时血压低于80 mmHg的发生率、初始碱缺失以及试验药物开始使用时间方面具有可比性。AT III组患者在最初4天共接受约20,000 IU的药物。通过该方案可使AT III水平达到130%至140%，而对照组的AT III浓度平均约为70%。在AT III组，第一天凝血酶原趋于升高，凝血酶原片段F1 + 2以及凝血酶 - AT III复合物趋于降低。然而，两组在部分凝血活酶时间、凝血酶原时间、血小板、纤溶酶原激活物抑制剂I、可溶性肿瘤坏死因子受体II、中性粒细胞弹性蛋白酶、白细胞介素（IL）-1受体拮抗剂、IL - 6和IL - 8方面未观察到差异。两个治疗组的死亡率（15%对5%）、呼吸衰竭发生率（55%对55%）、机械通气时间（13天对12天）以及外科重症监护病房住院时间（19天对21天）也相似。然而，接受AT III治疗的患者器官衰竭持续时间较短。
早期大剂量给予严重钝性创伤患者AT III似乎并不能减轻创伤后炎症反应或显著改善预后。
