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OBJECTIVE To evaluate the effects of short-term, high-volume hemofiltration (STHVH) on hemodynamic and metabolic status and 28-day survival in patients with refractory septic shock. DESIGN Prospective, interventional. SETTING Intensive care unit (ICU), tertiary institution. PATIENTS Twenty patients with intractable cardiocirculatory failure complicating septic shock, who had failed to respond to conventional therapy. INTERVENTIONS STHVH, followed by conventional continuous venovenous hemofiltration. STHVH consisted of a 4-hr period during which 35 L of ultrafiltrate is removed and neutral fluid balance is maintained. Subsequent conventional continuous venovenous hemofiltration continued for at least 4 days. MEASUREMENTS AND MAIN RESULTS Cardiac index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery, mixed venous oxygen saturation, arterial pH, and lactate were measured serially. Fluid and inotropic support were managed by protocol. Therapeutic endpoints were as follows during STHVH: a) by 2 hrs, a > or =50% increase in cardiac index; b) by 2 hrs, a > or =25% increase in mixed venous saturation; c) by 4 hrs, an increase in arterial pH to >7.3; d) by 4 hrs, a > or =50% reduction in epinephrine dose. Patients who attained all four goals (11 of 20) were considered hemodynamic "responders"; patients who did not (9 of 20) were considered hemodynamic "nonresponders." There were no differences in baseline hemodynamic, metabolic, and Acute Physiology and Chronic Health Evaluation and Simplified Acute Physiology Scores between responders and nonresponders. Survival to 28 days was better among responders (9 of 11 patients) than among nonresponders (0 of 9). Factors associated with survival were hemodynamic-metabolic response status, time interval from ICU admission to initiation of STHVH, and body weight. CONCLUSIONS These data suggest that STHVH may be of major therapeutic value in the treatment of intractable cardiocirculatory failure complicating septic shock. Early initiation of therapy and adequate dose may improve hemodynamic and metabolic responses and 28-day survival.

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 ± 109 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” ultra-filtrate (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. (Crit Care Med 1993; 21:914–924)

To evaluate the effect of hemofilter pore size on the efficacy of continuous arteriovenous hemofiltration (CAVH) in improving morbidity and mortality in an immature swine model of Staphylococcus aureus-induced septicemia.Prospective, randomized study with age-matched controls.Biomedical research facility.Fourteen 4 to 8-wk-old, weaned Poland-China swine, weighing 5 to 10 kg.Spontaneously breathing, ketamine-sedated swine (4 to 8 wks of age) were given an intravenous lethal dose of live S. aureus. Animals were then filtered with either a 50-kilodalton (kD) pore size filter (control) or a 100-kD pore size filter (experimental). No animals received antibiotics.Physiologic, biochemical, and hematologic parameters were measured in all animals every 1 to 3 hrs. Animals were monitored continuously and survival time (hr) was recorded (permanent survival = 168 hrs/7 days). Animals filtered with the 100-kD filter survived significantly longer than control animals (103 +/- 18 [SEM] vs. 56 +/- 9 hrs). The 100-kD-filtered group had one permanent survivor (168 hrs). Protein concentration of the ultrafiltrate obtained from the 100-kD-filtered animals was eight-fold higher than control ultrafiltrate. The protein removed did not contain a high percentage of albumin (as determined by autoanalyzer methods). No significant differences were seen in any of the other measured parameters.CAVH significantly improved survival in swine with S. aureus-induced sepsis. The superior performance of the 100-kD filter vs. the 50-kD filter suggests that higher molecular weight mediators that are not removed efficiently by the 50-kD filter may be responsible for the morbidity and mortality seen in this model of sepsis. These mediators may be removed in greater proportion by our customized (100-kD pore size) filter.