Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the effect of pentoxifylline on organ dysfunction, survival, and mediator response in patients with severe sepsis.

DESIGN: Randomized, double-blind, placebo-controlled study.

SETTING: Surgical intensive care units at 2 university hospitals.

PATIENTS: Fifty-one surgical patients with severe sepsis were randomized to receive pentoxifylline continuously (27 patients) or saline infusion as placebo (24 patients).

INTERVENTIONS: PATIENTS received pentoxifylline (1 mg/kg of body weight per hour; maximum, 1800 mg/d) during 28 days or until they were discharged from the intensive care unit or died.

MEASUREMENTS AND MAIN RESULTS: Vital signs and organ function were determined at diagnosis; daily from day 1 to 7; on days 10, 14, 17, 21, and 24; and 28 days after diagnosis of sepsis. There were no differences in characteristics of patients at diagnosis in the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (mean+/-SEM, 17+/-4 points for the pentoxifylline group and 18+/-5 points for the placebo group), the multiple organ dysfunction score (mean+/-SEM, 11.0+/-0.8 vs 11.8+/-1.0 points), tumor necrosis factor alpha and interleukin 6 bioactivity, serum endotoxin levels, or organ dysfunction. At study entrance, 23 of 27 patients in the pentoxifylline group and 21 of 24 patients in the placebo group experienced septic shock. No adverse effects of pentoxifylline treatment were observed. The 28-day mortality rate was 30% (8/27) in pentoxifylline-treated patients and 33% (8/24) in the placebo group. Hospital mortality was 41% (11/27) in the pentoxifylline group and 54% (13/24) in the placebo group. The multiple organ dysfunction score decreased in patients receiving pentoxifylline 4 days after diagnosis of sepsis compared with placebo-treated patients; a significant difference was reached on day 14 (P<.05; Student t test, Bonferoni correction). The PaO2/FIO2 (fraction of inspired oxygen) ratio was significantly improved in pentoxifylline-treated patients on days 14 and 17 (P<.05), and the pressure-adjusted heart rate was significantly improved on day 6 (P<.05) compared with the placebo group. Serum endotoxin levels, tumor necrosis factor alpha and interleukin 6 bioactivity were not different between the groups during the study.

CONCLUSIONS: Continuous intravenous administration of pentoxifylline beneficially influenced cardiopulmonary dysfunction in patients with sepsis without adverse effects. Larger trials are needed to evaluate the efficacy in improving organ function in relation to the outcome for patients with severe sepsis.