Changes in plasminogen activator inhibitor-1 (PAI-1) in patients with severe sepsis or septic shock

Introduction

For septic shock, especially that caused by infection with Gram-negative bacteria, endotoxin adsorption (direct hemoperfusion using polymyxin B fixed fiber: PMX-DHP) is regarded as an effective method of treatment in Japan. In 27 patients who were admitted to ICU and underwent PMX-DHP for severe sepsis or septic shock, the kinetics of PAI-1 were determined, and compared between the group with a high endotoxin level of 10 pg/ml or more just before the initiation of PMX-DHP and the group with a normal endotoxin level of less than 10 pg/ml. Furthermore, the relations between PAI-1 and other mediators were examined.

Method

Hemoperfusion using polymyxin B fixed fiber was performed by inserting a double-lumen catheter into the femoral or subclavian vein, at a blood flow rate of 80–100 ml/min. Determinations of PAI-1 and various cytokines including interleukin-6 (IL-6), interleukin-10 (IL-10) and interleukin-1 receptor antagonist (IL-1ra) were performed by enzyme linked immunosorbent assay (ELISA) just before the initiation, just after the completion, and 24 hours after the completion of PMX-DHP.

Subjects' backgrounds and underlying diseases

The number of patients was 12 in the normal level endotoxin group (Group N) and 15 in the high level endotoxin group (Group H). No significant difference was found in age. Regarding sex difference, females were dominant in Group N, while males were dominant in Group H. For other items including the number of pertinent items, septic severity score, APACHE-II score and MOF score, Group H had higher values in general. Most of the patients the underlying disease was sepsis caused by abdominal infection. Concerning the outcome after 4 weeks, nine (75%) out of 12 patients in Group N survived and 11 (73%) out of 15 patients survived in Group H, without significant difference.

Results

Changes in PAI-1 corresponding to endotoxin level

PAI-1 before the initiation of PMX-DHP was 416 ± 500 ng/ml in Group H, while that in Group N was 172 ± 141 ng/ml, showing a 2.4-fold higher tendency in Group H than in Group N. However, the correlation between PAI-1 and endotoxin level before the initiation, just after completion, and 24 hours after completion of PMX-DHP was not significant. PAI-1 level just after completion of PMX-DHP was 104 ± 12 and 362 ± 559 ng/ml in Group N and Group H, respectively, showing a decreasing tendency and a greater decrease in Group H after 24 hours.

Relations between PAI-1 and other cytokines

At any period before the initiation, just after completion, and 24 hours after the completion of PMX-DHP, a significant positive correlation was found between PAI-1 and IL-6, indicating the possible role of IL-6 in controlling the kinetics of PAI-1. As in the case of IL-6, a significant positive correlation was also found, at any period, between PAI-1 and IL-10, an anti-inflammatory cytokine. A significant positive correlation was found, at periods before initiation and just at completion of PMX-DHP, but not after 24 hours.

Conclusion

Septic-shock patients who underwent endotoxin adsorption treatment were subjected to examination focusing on the changes in PAI-1. PAI-1 level was apt to be higher in the high endotoxin level group, and had a tendency to decrease in patients with successful PMX treatment.