van Veen Suzanne Q, Levi Marcel, van Vliet Arlène K, Florquin Sandrine, van Gulik Thomas M, Boermeester Marja A
Department of Surgery (Surgical Laboratory), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Crit Care Med. 2006 Nov;34(11):2799-805. doi: 10.1097/01.CCM.0000243795.04284.2A.
During peritonitis, intra-abdominal fibrin entraps bacteria and hampers their elimination. Systemic administration of anticoagulant activated protein C improves survival in patients with severe sepsis, but its precise mode of action is unclear. This study in polymicrobial peritonitis assessed the effects of local activated protein C administration in peritoneal lavage fluid on coagulation, fibrinolysis, and survival.
Prospective, randomized study.
University-based research laboratory.
C57BL/6 mice.
Twenty-four hours after induction of peritonitis by cecal ligation and puncture, mice underwent peritoneal lavage with activated protein C (1.0 microg/mL) or saline. Peritoneal lavage fluid, blood, and lungs were sampled after 24, 48, or 72 hrs (n = 8/group/time point). For survival analysis, maximum observation was 96 hrs (n = 22/group). Clotting time, tissue factor expression, thrombin-antithrombin complexes, fibrin degradation products (D-dimers), plasminogen activator, and plasminogen activator inhibitor were used to assess coagulation and fibrinolysis responses.
Activated protein C lavage reduced abdominal bacterial load, abdominal and pulmonary clotting times, D-dimers (p < .05 vs. saline), pulmonary tissue factor expression, and fibrin depositions, without clear effects on systemic thrombin generation. Activated protein C lavage decreased plasma and abdominal tissue plasminogen activator levels with increased inhibitor plasminogen activator inhibitor-1 levels (p < .05) but had reverse effects on pulmonary fibrinolysis. Survival improved from 55% (saline) to 80% after intra-abdominal activated protein C administration (p = .03).
Peritoneal lavage with activated protein C may rebalance coagulation and fibrinolysis within compartments and improve survival in polymicrobial peritonitis.
在腹膜炎期间，腹腔内纤维蛋白会困住细菌并阻碍其清除。全身性给予抗凝剂活化蛋白C可提高严重脓毒症患者的生存率，但其确切作用方式尚不清楚。本项关于多微生物性腹膜炎的研究评估了在腹腔灌洗液中局部给予活化蛋白C对凝血、纤维蛋白溶解和生存的影响。
前瞻性随机研究。
大学研究实验室。
C57BL/6小鼠。
通过盲肠结扎和穿刺诱导腹膜炎24小时后，小鼠接受用活化蛋白C（1.0微克/毫升）或生理盐水进行的腹腔灌洗。在24、48或72小时后采集腹腔灌洗液、血液和肺样本（每组/每个时间点n = 8）。进行生存分析时，最大观察时间为96小时（每组n = 22）。使用凝血时间、组织因子表达、凝血酶 - 抗凝血酶复合物、纤维蛋白降解产物（D - 二聚体）、纤溶酶原激活剂和纤溶酶原激活剂抑制剂来评估凝血和纤维蛋白溶解反应。
活化蛋白C灌洗降低了腹腔细菌载量、腹腔和肺的凝血时间、D - 二聚体（与生理盐水相比，p < 0.05）、肺组织因子表达和纤维蛋白沉积，对全身凝血酶生成无明显影响。活化蛋白C灌洗降低了血浆和腹腔组织纤溶酶原激活剂水平，同时抑制剂纤溶酶原激活剂抑制剂 - 1水平升高（p < 0.05），但对肺纤维蛋白溶解有相反作用。腹腔内给予活化蛋白C后，生存率从55%（生理盐水组）提高到80%（p = 0.03）。
用活化蛋白C进行腹腔灌洗可能会重新平衡各腔室内的凝血和纤维蛋白溶解，并提高多微生物性腹膜炎的生存率。
