Therapie der Pseudomonas aeruginosa-Sepsis mit rhG-CSF (Filgrastim) unter besonderer Berücksichtigung der hämodynamischen Veränderungen und des klinischen Verlaufes : eine experimentelle Studie am nicht anästhesierten, invasiv instrumentierten Schwein

Abstract

In this study the effect of rhG-CSF on the Gram-negative sepsis in the not sedated pig were investigated. The clinical course, hemodynamic parameters, the blood gas conditions and different mediators were considered. For a simulation of the clinical situation the growth factor was given 3 hours after the induction of a P. aeruginosa septicemia and repeated every 24 h afterwards. We used 7 animals in the G-CSFgroup and 10 in the control group. The observation period was appointed to 120 hours. 5 animals of the G-CSF group and 5 of the controls attained the endpoint (71 % and 50 % respectively). Those animals who received the growth factor, responded within 24 h of the first application with a increased leukocyte count in the peripheral blood compared with the control. The level reached 140 % of the baseline count in this group. Apart from these increase we could not ascertain any significant distinctions in the investigated parameters between the control and the G-CSF group.

The neutrophilic granulocyte are valid as the main effectors of the organ injury in a septicemic disorder. In these occurence they are stimulated by the mediators endotoxin, TNF-?, IL-1 and others to adhesion and emigration in the tissue as well as to the production and liberation of cytotoxic enzymes and radicals. This is primary manifestated in the lung.

In the investigated G-CSF group the leukocyte count increased in the last phase up to 162 % of the control level. Nevertheless we could not find out any enhanced lung injuries. Presumable this is mainly caused by the changed reactions of the induced granulocytes, wich are sure stimulated by the growth hormone, but which as well shed the adhesion molecules CD62L from their surface, so that they are less adhesive to the endothelium.

So with the therapeutical application of G-CSF in the non-neutropenic pig we could not show any negative effects, but we also do not have benefit to the Gram-negative sepsis. By this aspect and in consideration of the high costs of such an additive therapy one should do without G-CSF in the non-neutropenic patient with Pseudomonas sepsis.