The role of plasminogen activator inhibitor 1 measurement with endotoxin adsorption therapy (PMX-DHP) for postoperative septic shock patients

Introduction

A polymyxin B immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was developed in Japan in 1994 and it has been used for treatment of endotoxemia or septic shock patients.

Materials and methods

All patients received an urgent operation due to intra-abdominal infection. In 88 cases treated with a poly-myxin B immobilized column through direct hemoperfusion (PMX-DHP), changes in hemodynamics, pulmonary oxygenation (PaO₂/FIO₂) and various mediators (IL-6, IL-8, IL-ra, plasminogen activator inhibitor 1 (PAI-1)) were examined before and after PMX-DHP, stratifying with the outcome (64 survivors and 24 who died). PMX-DHP was performed through a double lumen catheter (11.5 Fr), placed in the femoral vein or internal jugular vein, at a blood flow rate of 80 ml/min using nafamostat mesilate as an anticoagulant for 2 hours.

Results

PMX-DHP significantly increased systemic arterial pressure and mean arterial pressure, with a greater increase in the survival group. Also, there appeared to be a trend for PaO₂/FIO₂ improvement as blood pressure increased. As the mechanism for improvement of pulmonary oxygenation by PMX-DHP has not been shown clearly, it remained to be examined further. PAI-1 values significantly decreased in the survivor group (from 436 ± 549 to 251 ± 283 ng/ml) immediately after PMX-DHP; also intracellular adhesion molecule-1 and endothelial leukocyte adhesion molecule-1 tended to decrease in both groups.

Discussion

PAI-1 is elevated by endotoxin, thrombin and cytokines, and is an indicator of vascular endothelial cell activation. In septic dissminated intravascular coagulation from Gram-negative bacilli, a massive amount of PAI-1 is produced on vascular endothelial cells along with elevation of cytokine production and coagulation activity. In addition, PAI-1, one of the fibrinolysis inhibitory factors, plays an important role in regulating fibrinolysis by inhibiting tissue plasminogen activator, which converts plasminogen to active plasmin on fibrin, to block unnecessary fibrinolysis.

Conclusion

The determination of PAI-1 may be a useful clinical parameter for predicting PMX-DHP efficacy.