[Gabexate mesilate (FOY), a new synthetic protease inhibitor, in the treatment of shock. An Italian multicenter study].

BACKGROUND

Circulatory shock has been accepted as a consequence of a chain of biochemical events beginning with production of proteases and ending with an uncontrolled generation of oxygen radicals.

OBJECTIVE

To evaluate the efficacy of gabexate-mesilate (FOY) in circulatory shock in man. Gabexate-mesilate is a new wide-range synthetic protease inhibitor that also has antioxidant properties.

DESIGN

Clinical multicenter study with open design that has been compared with some Japanese controlled studies performed using identical parameters and very similar protocols.

EXPERIMENTS

59 shocked patients were treated with FOY in 9 italian intensive therapy units. Circulatory shock was traumatic (n = 14), traumatic-hemorrhagic (n = 25), septic (n = 11) or of mixed type (n = 9). Evaluation of seriousness of shock on beginning of therapy and during the follow-up period was performed on the basis of the same "shock score" (Ogawa and Fujita, Jap J Surg 12:122, 1982) that was used in Japanese clinical studies on FOY in shock. 1.45 mg/kg/hour of FOY were injected i.v. during 48 hours. Conventional therapy was permitted but steroids and aprotinin were excluded. The follow-up period was 9 days.

RESULTS

8 patients died. The mean initial score of the survivors was 8.2; after 8 hours it was 5.0 and after 12 it was 4.0. No adverse reactions were reported. The above quoted survival was greater than that of Japanese studies although the initial score was quite the same. However these studies were controlled and demonstrated gabexate-mesilate to be significantly more active in shock therapy than placebo. They also demonstrated an activity of FOY greater than that of aprotinin when shock was associated to acute respiratory insufficiency and to coagulopathies.

CONCLUSIONS

Gabexate mesilate might be useful in therapy of circulatory shock due to its wide-range inhibition of proteases and to its antioxidant properties.