Hirose Tomoya, Ogura Hiroshi, Takahashi Hiroki, Ojima Masahiro, Jinkoo Kang, Nakamura Youhei, Kojima Takashi, Shimazu Takeshi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871 Japan.
J Intensive Care. 2018 Jul 4;6:37. doi: 10.1186/s40560-018-0309-5. eCollection 2018.
C1 inhibitor (C1-INH), which belongs to the superfamily of serine protease inhibitors, regulates the complement system and also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1-INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective of this study was to clarify the serial change of C1-INH in patients with sepsis and evaluate the relationship with the shock severity.
This was a single-center, prospective, observational study. We serially examined C1-INH activity values (normal range 70-130%) in patients with sepsis admitted into the intensive care unit of the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between January 2014 and August 2015. We defined "refractory shock" as septic shock unresponsive to conventional therapy such as adequate fluid resuscitation and vasopressor therapy to maintain hemodynamics.
Serial changes of C1-INH were evaluated in 40 patients with sepsis (30 men, 10 women; 30 survivors, 10 non-survivors; mean age, 70 ± 13.5 years). We divided the patients into three groups: non-shock group ( = 14), non-refractory shock group ( = 13), and refractory shock group ( = 13: 3 survivors, 10 non-survivors). In the non-shock group, C1-INH was 107.3 ± 26.5% on admission and 104.2 ± 22.3% on day 1, and it increased thereafter to 128.1 ± 26.4% on day 3, 138.3 ± 21.2% on day 7, and 140.3 ± 12.5% on day 14 ( < 0.0001). In the non-refractory shock group, C1-INH was 113.9 ± 19.2% on admission, 120.2 ± 23.0% on day 1, 135.7 ± 19.9% on day 3, 138.8 ± 17.2% on day 7, and 137.7 ± 10.7% on day 14 ( < 0.0001). In the refractory shock group, C1-INH was 96.7 ± 15.9% on admission, 88.9 ± 22.3% on day 1, 119.8 ± 39.6% on day 3, 144.4 ± 21.1% on day 7, and 140.5 ± 24.5% on day 14 ( < 0.0001). The difference between these three groups was statistically significant ( < 0.0001). C1-INH in non-survivors did not increase significantly during their clinical course ( = 0.0690).
In refractory shock patients with sepsis, the values of C1-INH activity were lower (especially in non-survivors) on admission and day 1 as compared with non-shock and non-refractory shock patients.
C1抑制剂（C1-INH）属于丝氨酸蛋白酶抑制剂超家族，可调节补体系统以及血浆激肽释放酶-激肽、纤维蛋白溶解和凝血系统。C1-INH的生物学活性可分为调节血管通透性和抗炎功能。本研究的目的是阐明脓毒症患者C1-INH的系列变化，并评估其与休克严重程度的关系。
这是一项单中心、前瞻性观察性研究。我们对2014年1月至2015年8月期间入住大阪大学医院（日本大阪）创伤与急性重症监护中心重症监护病房的脓毒症患者的C1-INH活性值（正常范围70-130%）进行了系列检测。我们将“难治性休克”定义为对充分液体复苏和血管升压药治疗等常规治疗无反应以维持血流动力学的脓毒性休克。
对40例脓毒症患者（30例男性，10例女性；30例幸存者，10例非幸存者；平均年龄70±13.5岁）的C1-INH系列变化进行了评估。我们将患者分为三组：非休克组（=14）、非难治性休克组（=13）和难治性休克组（=13：3例幸存者，10例非幸存者）。在非休克组中，入院时C1-INH为107.3±26.5%，第1天为104.2±22.3%，此后在第3天升至128.1±26.4%，第7天为138.3±21.2%，第14天为140.3±12.5%（<0.0001）。在非难治性休克组中，入院时C1-INH为113.9±19.2%，第1天为120.2±23.0%，第3天为135.7±19.9%，第7天为138.8±17.2%，第14天为137.7±10.7%（<0.0001）。在难治性休克组中，入院时C1-INH为96.7±15.9%，第1天为88.9±22.3%，第3天为119.8±39.6%，第7天为144.4±21.1%，第14天为并140.5±24.5%（<0.0001）。这三组之间的差异具有统计学意义（<0.0001）。非幸存者的C1-INH在其临床过程中未显著增加（=0.0690）。
在脓毒症难治性休克患者中，与非休克和非难治性休克患者相比，入院时和第1天的C1-INH活性值较低（尤其是在非幸存者中）。
