The effect of extracorporeal blood purification on clinical outcomes in sepsis is assumed to be related to modulation of plasma cytokine concentrations. To test this hypothesis directly, we treated rats that had a cecal ligation followed by puncture (a standard model of sepsis) with a modest dose of extracorporeal blood purification that did not result in acute changes in a panel of common cytokines associated with inflammation (TNF-α, IL-1β, IL-6, and IL-10). Pre- and immediate post-treatment levels of these cytokines were unchanged compared to the sham therapy of extracorporeal circulation without blood purifying sorbent. The overall survival to 7 days, however, was significantly better in animals that received extracorporeal blood purification compared to those with a sham procedure. This panel of common plasma cytokines along with alanine aminotransferase and creatinine was significantly lower 72 h following extracorporeal blood purification compared to sham-treated rats. Thus, the effects of this procedure on organ function and survival do not appear to be due solely to immediate changes in the usual measured circulating cytokines. These results may have important implications for the design and conduct of future trials in sepsis including defining alternative targets for extracorporeal blood purification and other therapies.
Summary: Artificial subtraction of fluids and solutes was evaluated in the course of acute and chronic heart failure when it became refractory to standard intensive medical treatment. A group of 19 patients (mean age 57 years), 9 with ischemic, 2 arnyloidotic, 4 valvular, and 4 idiopathic cadiomyopathy, were treated. In 17 patients extracorporeal ultrafiltration (UF) by means of a polysulfonate ultrafilter was adopted along 125 sessions (105 assisted by a roller pump and 20 as a slow continuous ultrafiltrate). In two patients continuous peritoneal dialysis was adopted. In every case UF was well tolerated. Ultrafiltmte volumes ranged from 1680 to 3500 ml for every session with corresponding Na losses ranging from 194 to 434 mEq/session. Improved clinical and functional status with reduction of edema was observed in 17 of 19 patients. In 12 patients UF could be discontinued due to restored response to diuretics; 5 of these patients could subsequently undergo heart surgery (1 transplant, 3 valve nplacement, 1 coronary bypass). The remaining 7 patients survived od medical therapy alone for an average of 228 days. In 7 of 19 cases, UF could not be discontinued, and these patients died after an average of 23 days of treatment. In conclusion, UF proved to be effective in eliminating salt-fluid overload and restoring response to medical treatment. Patients who are potential surgical candidates !kern to be the most suitable for UF.
Sepsis is a systemic response to infection characterized by increased production of imflammatory mediators including cytokines. Increased production of cytokines such as interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor (TNF) can have deleterious effects. Removal of cytokines via adsorption onto porous polymer substrates using an extracorporeal device may be a potential therapy for sepsis. We are developing a cytokine adsorption device (CAD) containing microporous polymer beads that will be used to decrease circulating levels of IL-6, TNF, and IL-10. In this paper we present a mathematical model of cytokine adsorption within such a device. The model accounts for macroscale transport through the device and internal diffusion and adsorption within the microporous beads. The analysis results in a simple analytic expression for the removal rate of individual cytokines that depends on a single cytokine-polymer specific parameter, Γ i . This model was fit to experimental data and the value of Γ i was determined via nonlinear regression for IL-6, TNF, and IL-10. The model agreed well with the experimental data on the time course of cytokine removal. The model of the CAD and the values of Γ i will be applied in mathematical models of the inflammatory process and treatment of patients with sepsis.
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