TITLE: Pentoxifylline in severe sepsis: a double-blind, randomized placebo-controlled study

  ABSTRACT:


BODY.FULL TEXT:
Pentoxifylline (POF) inhibits macrophage production of tumor necrosis factor alpha (TNF) as a central mediator in sepsis. To evaluate the therapeutic effect of POF in patients with sepsis a prospective, double-blind, placebo-controlled study in two centers (Lübeck, Kiel) was performed. 51 patients were included and randomized to receive POF continuously (1 mg/kg bw/h i.v.) or saline solution as placebo over 28 days maximally or until patients were discharged from ICU or died. Bioactivity of TNF and interleukin (IL)-6, MOF-score according to Goris as well as organ function were determined at diagnosis, daily from day 1 to 7, on day 10, 14, 17, 21, 24 and 28 after diagnosis of sepsis. There were no differences in patients characteristics at diagnosis concerning APACHE II score [17 ± 4 (mean ± SD)] for POF and 18 ± 5 points for placebo), MOF-score (10.5 vs 10.7) or organ function. At study entrance 23 of 27 patients in the POF-group and 21/24 in the placebo-group had septic shock. No adverse effects of POF-treatment were observed. The 28 day mortality rate was 30% (8/27) in POF treated patients and 33% (8/24) in the control group. Hospital mortality was 41% (11/27) and 54% (13/24). Serum concentrations of TNF and IL-6 were not significantly different throughout the evaluation. MOF-score was lower in POF treated patients after day 4 compared to placebo treated patients which reached significant differences on day 14 and 21 (P < 0.05, unpaired t-test). PaO2/FioO2-ratio was significantly improved in POF treated patients from day 10 (266 ± 132) to day 21 (346 ± 142) compared to the placebo group (201 ± 161 vs 221 ± 112, P < 0.05 and P < 0.01 on day 14 and 17). Pressure-adjusted heart rate (HR×CVP/MAP) was significantly improved from day 6 to day 10 (P < 0.05) in patients treated with POF compared to the control group. A multi-center trial is needed to evaluate the efficacy in improving organ function and outcome in severe sepsis.

Question: Compared to Placebo what was the result of Pentoxifylline  on Pressure-adjusted heart rate improvement ?
Evidence: Serum concentrations of TNF and IL-6 were not significantly different throughout the evaluation.
Answer: significantly increased