CONTINUOUS VENOVENOUS HEMOFILTRATION WITH DIALYSIS REMOVES CYTOKINES FROM THE CIRCULATION OF SEPTIC PATIENTS

Objectives. To determine whether continuous veno-venous hemofiltration with dialysis leads to extraction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and removal rates of these cytokines and their effect on serum cytokine concentrations. Design: Prospective, controlled study of TNF-alpha and IL-1beta extraction by continuous veno-venous hemofiltration with dialysis in patients with septic acute renal failure. Setting: Intensive care unit of a tertiary institution. Patients. Eighteen critically ill patients with sepsis and acute renal failure. Control group of six patients experiencing an acute illness while undergoing chronic hemodialysis. Interventions: Collection of blood samples before continuous veno-venous hemofiltration with hemodialysis. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 hrs of treatment. Measurements and Main Results: TNF-alpha and IL-1beta concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extraction were calculated and compared with a control group. TNF-alpha was detected in 66.6% of serum samples of patients with septic acute renal failure; IL-1beta was detected in 55% of patients' sera samples. Both TNF-alpha and IL-1beta were cleared by the hemofilter during continuous veno-venous hemofiltration with dialysis. The mean clearance for TNF-alpha was 30.7 L/day (95% confidence interval 22.4 to 39) with a daily mean excretion of 14.1 mug (95% confidence interval 1.7 to 26.5). Mean IL-1beta clearance was 36.1 L/day (95% confidence interval 25.4 to 46.8) equivalent to a mean daily IL-1beta excretion of 1 mug (95% confidence interval 0.9 to 1.1). No measurable concentrations of TNF-alpha or IL-1beta were found in the serum or ultrafiltrate specimens of control patients. Conclusions: These findings demonstrate that continuous veno-venous hemofiltration with dialysis can remove both TNF-alpha and IL-1beta from the circulation of septic, critically ill patients. This cytokine extraction may prove to be of benefit in attenuating the progression of multiple organ dysfunction in patients with sepsis-associated renal failure, who are receiving continuous veno-venous hemofiltration with dialysis. This potential benefit of existing hemofiltration therapies supports their preferential implementation in patients with renal failure associated with severe sepsis. These observations may stimulate the modification of filtration membrane design seeking to specifically augment the clearance from the circulation of a variety of such cytokines.