Acute and high-dose therapy of urinary trypsin inhibitor could inhibit vascular endothelial cell disorders in critical illness

Introduction

Urinary trypsin inhibitor (UTI) (MIRACLID^®, Mochida Corp., Tokyo, Japan), an elastase inhibitor extracted from human urine, has been used to treat for patients with acute pancreatitis or acute circulatory failure since more than 15 years ago in Japan.

Objective

The current study was performed in order to evaluate the efficacy of UTI for vascular endothelial disorders in critical illness.

Materials and methods

Thirteen severe patients, who had an APACHE II score above 20 at transportation to our emegency room, were elected and randomly assigned to either a treated group or a control group. The number of patients in the treated group was five and eight patients were in the untreated group. Maximum dose of UTI (30,000 U/ml) were administrated to patients in the treated group at the emergency room. After admission in the ICU, the neutrophil elastase level, IL-6 level, thrombomodulin (TM) level, protein C level and UTI level in plasma were examined daily until the 7th day after hospitalization. Values are expressed as mean ± SD. An unpaired Student's t test was used and P < 0.05 was considered statistically significant.

Results

In the untreated group, the UTI level in plasma at the 7th day after hospitalization was siginificantly higher than that in the treated group (96.9 ± 44.4 vs 15.6 ± 6.5 U/ml, P < 0.05). Also, the TM level was also significantly different between the untreated group and the treated group (6.0 ± 2.4 vs 3.6 ± 1.4 FU/l, P < 0.05) at the 7th day. Other examination values showed no significant differences between the two groups during their clinical courses.

Conclusion

The half-time of UTI is very short (about 40 min) and the plasma level linear decreases until 3 hours after its administration. The difference of UTI level on the 7th day was considered as spontaneous UTI. And vascular endothelial disorders were recognized in the higer UTI level group at the same day, but this group was the untreated group. This study proposes it i important for high-dose administration of UTI at a very acute phase in critical illness to inhibit the vascular endothelial disorders.