Enhancement of neutrophil function by in vivo filgrastim treatment for prophylaxis of sepsis in surgical intensive care patients

Abstract

Purpose: To determine the kinetics of leukocyte counts and of oxygen radical production of neutrophils from postoperative/posttraumatic patients with or without infusion of filgrastim (recombinant human granulocyte colony-stimulating factor, rhG-CSF) as prophylaxis against sepsis. Methods: Twenty postoperative/ posttraumatic patients with a Therapeutic Intervention Scoring System (TISS) score greater than 30 were included in this study. In the 10 patients of the study group, filgrastim (1 μg/kg/d) was infused continuously within the first 3 days and tapered to 0.5 μg/kg/d on the following 4 days or until discharge from the surgical intensive care unit. Ten patients without administration of filgrastim served as controls. Oxygen radical production of isolated neutrophils of these patients was tested by N-formyl-methionyl-leucyl-phenylalanine (FMLP)- and zymosan-induced chemiluminescence from serial blood samples, taken until the 16th postoperative day. Results: Compared with the first postoperative day, in vitro FMLP-induced neutrophil chemiluminescence was significantly increased during the following 4 postoperative days in the patients with filgrastim infusion; however, only during the first 2 postoperative days in the control group. The increase in the FMLP-induced neutrophil chemiluminescence was significantly greater ( P < .05) in the study group than in the control group on the third and on the fourth postoperative day. Tapering of filgrastim by 0.5 μg/kg/d in the study group resulted in a reduction of FMLP-induced neutrophil oxygen radical production within 48 hours. In contrast, zymosan-induced neutrophil chemiluminescence was not measurably affected in both groups. Leukocyte count of the study group significantly ( P < .05) exceeded the leukocyte count of the control group from the third up to the 10th postoperative day. None of the patients treated with filgrastim developed sepsis; however, three patients within the control group did. Conclusions: Prolonged enhancement of neutrophil count and function induced by rhG-CSF may be useful in the prophylaxis of sepsis in posttraumatic/postoperative patients at high risk of sepsis.