CONTINUOUS ARTERIOVENOUS HEMOFILTRATION THERAPY FOR STAPHYLOCOCCUS-AUREUS-INDUCED SEPTICEMIA IN IMMATURE SWINE

Objectives. The goals of this study were: a) to evaluate the efficacy of controlled, continuous arteriovenous hemofiltration in improving morbidity and mortality rates in an immature swine model of Staphylococcus aureus-induced septicemia; b) to determine if ultrafiltrate from septic animals contained mediators that produce pathophysiologic changes observed in untreated S. aureus septic pigs. Design: Prospective, randomized, controlled study with age-matched controls. Setting. U.S. Department of Agriculture-licensed biomedical research facility. Subjects: Sixty-five weaned Poland-China swine (4 to 6 wks of age; 5 to 10 kg). Interventions. Part 1: Animals received a lethal dose of live S. aureus (8 x 10(9) colony-forming units/kg) over 1 hr. The three treatment groups included: hemofiltration group 1 (eight filtered, eight nonfiltered animals), plasma filtration fraction = 5.5%; hemofiltration group 2 (six filtered, six nonfiltered animals), filtration fraction = 16.6%; and hemofiltration group 3 (six filtered, six nonfiltered animals), filtration fraction = 33.4%. A control, nonseptic group of animals (n = 4) was filtered to obtain 'clean' ultrafiltrate (hemofiltration group 4). Part 2: Sterile ultrafiltrate concentrate batches obtained from each group of filtered, septic animals were concentrated and infused into healthy, nonseptic pigs (reinfusion groups 1 through 3). Measurements and Main Results. Physiologic, biochemical, and hematologic variables were measured in all animals every 1 to 3 hrs. Overall length of survival was also recorded. In hemofiltration groups 1 through 3, filtered animals survived significantly longer than matched, nonfiltered (sham-filtered) animals. Increments in survival time increased directly with filtration fraction. Ultrafiltrate concentrate from septic pigs produced death (LD41) and disease similar to those rates observed in untreated S. aureus-septic pigs. Infusion of clean ultrafiltrate concentrate produced no response. Conclusions: Continuous arteriovenous hemofiltration significantly improved survival rates in swine with S. aureus-induced sepsis. Resultant ultrafiltrate concentrate contained mediators responsible for some pathophysiologic responses observed in this animal model.