EFFECTS OF PENTOXIFYLLINE ON CIRCULATING CYTOKINE CONCENTRATIONS AND HEMODYNAMICS IN PATIENTS WITH SEPTIC SHOCK - RESULTS FROM A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY

Objective: To determine whether a continuous intravenous infusion of p entoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. Design: A prospective, randomized, double-blind, placebo contr olled study. Setting: Medical intensive care unit in a university hosp ital. Patients: Sixteen patients with septic shock. Interventions: Pat ients were randomly assigned to receive either pentoxifylline (1 mg/kg ) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or place bo (n = 8). Measurements and Main Results: Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoass ays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELIS A) and pentoxifylline concentrations by highperformance liquid chromat ography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline treated patients, at 24 hrs, ser um concentrations of TNF were significantly lower compared with contro ls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concen trations of IL-6 and IL-8 did not differ between the two treatment gro ups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxif ylline concentrations were 1544 +/- 241 ng/mL after the initial dose, and 5776 +/- 1781 ng/mL at the end of the 24 hr infusion. Five patient s in the pentoxifylline group and four patients in the placebo group d ied. Conclusions: Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Furt her studies are needed to determine if pentoxifylline's ability to low er circulating TNF concentration without altering hemodynamics will im prove outcome in septic shock.