Objective: To test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. Design: Prospective, pilot, crossover clinical trial. Setting: General intensive care unit in a teaching hospital. Subjects: Ten patients with hyperdynamic septic shock. Interventions: Patients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor-α (TNF-α) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-α production from normal human adherent monocytes incubated with patients' plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. Results: Mean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p = .001). There was an average decrease of norepinephrine requirement of 0.08 μg/kg/min with treatment A and 0.0049 μg/ kg/min with treatment B (p = .003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-α production from patients' whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p = .009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-α by 1 × 10 6 cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p = .019) and after incubation with anti-interleukin-10 monoclonal antibodies (p = .028). Conclusions: In patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.
- Tumor necrosis factor-α