Serial change of C1 inhibitor in patients with sepsis: a prospective observational study

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (n = 14), non-refractory shock group (n = 13), and refractory shock group (n = 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 (p < 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 (p < 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 (p < 0.0001). The difference between these three groups was statistically significant (p < 0.0001). C1-INH in non-survivors did not increase significantly during their clinical course (p = 0.0690). CONCLUSIONS: 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.