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      Intermittent High-Permeability Hemofiltration Modulates Inflammatory Response in Septic Patients with Multiorgan Failure

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          Background/Aim: Continuous venovenous hemofiltration with high-permeability hemofilters is a novel approach in the adjuvant therapy of septic patients. High-permeability hemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether intermittent high-permeability hemofiltration has an immunomodulatory effect on polymorphonuclear leukocytes and mononuclear cells. Methods: Twenty-eight septic patients with acute renal failure were randomly allocated to either receive intermittent high-permeability or conventional hemofiltration. Intermittent high-permeability hemofiltration consisted of a daily 12-hour course of high-permeability hemofiltration alternated by conventional hemofiltration. For high-permeability hemofiltration, a newly developed high-flux polyamide membrane (P2SH) with a nominal cutoff point of 60 kD was used. For conventional hemofiltration a high-flux polyamide hemofilter (Polyflux 11S, cutoff point 30 kD) was used. Results: The polymorphonuclear leukocyte phagocytosis activity before starting hemofiltration was almost double the rate of healthy controls in both groups (p < 0.001). The phagocytosis rate decreased significantly during the course of intermittent high-permeability hemofiltration (p < 0.05), whereas the values remained unchanged in the conventional hemofiltration group. Incubation of high-permeability filtrates with blood from healthy donors resulted in a significant induction of phagocytosis (p < 0.001), whereas conventional filtrates had no phagocytosis-stimulating effects. In addition, incubation of healthy-donor mononuclear cells with high-permeability but not conventional filtrates resulted in a significant tumor necrosis factor alpha release (p < 0.001). Conclusions: Intermittent high-permeability hemofiltration is a novel extracorporeal elimination modality which exhibits immunomodulatory effects on leukocytes, attenuating polymorphonuclear neutrophil phagocytosis. Further studies are necessary to elucidate whether these effects translate in a clinical improvement in patients suffering from sepsis.

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          Most cited references 6

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          Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies.

          Limited health care budgets have raised the issue of how much therapy should be dedicated to critically ill patients with multiorgan and acute renal failure (ARF). No data are available on patients with ARF after hospital discharge. We assessed long-term survival and quality of life after discharge. Nine hundred seventy-nine patients with ARF who needed continuous renal replacement therapies were analyzed retrospectively. Contact was achieved by questionnaires assessing health status and mental and physical well-being. The in-hospital mortality rate was 69% (n = 678). Postdischarge information was obtained from 89% (n = 267). Kaplan-Meier analyses showed surprisingly good postdischarge survival. Discharged patients had a 77% probability to survive the first 6 months. Those who did so had a probability of 89% to survive the following 6 months. After 5 years, the survival probability was 50%. Age and more than one comorbidity before hospitalization were associated with significantly lower postdischarge survival. Seventy-seven percent of questionnaire responders assessed their current health status as good to excellent, 57% were self-sustaining, and 49% stated that their quality of life had improved. Renal insufficiency remained in 41%, whereas 10% required chronic dialysis therapy. ARF is associated with a high in-hospital mortality rate. Nevertheless, patients leaving the hospital had a reasonable survival rate and good quality of life. We conclude that aggressive intensive care unit treatment is justified in these patients. Copyright 2002 by the National Kidney Foundation, Inc.
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            Effects of filter pore size on efficacy of continuous arteriovenous hemofiltration therapy for Staphylococcus aureus-induced septicemia in immature swine.

             Laura Pryor,  P Lee,  H Weger (1998)
            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.
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              Super high flux hemofiltration: a new technique for cytokine removal.

              To test whether hemofiltration using a hemofilter with large pores (super high flux hemofiltration) achieves effective cytokine removal. : Ex vivo study. Laboratory of an intensive care unit in a tertiary hospital. Five healthy volunteers. Blood was spiked with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore polyamide super high flux hemofilter (nominal cut-off point: 100 kDa). Hemofiltration was conducted at 1 l/h or 6 l/h of ultrafiltrate flow. Samples were taken from the arterial, venous and ultrafiltration sampling ports. Sieving coefficients (SC) above 0.6 were achieved for interleukin (IL)-1beta, IL-6 and IL-10 and SCs above 0.3 were achieved for IL-8 and TNF-alpha at 1 l/h. SCs of all cytokines (except IL-1) were reduced when the ultrafiltration rate was increased from 1 l/h to 6 l/h ( p<0.01), but cytokine clearances still increased ( p<0.01). The highest SC for albumin was 0.1 at 1 l/h and fell to 0.01 at 6 l/h. No adsorption of cytokines and albumin was observed. High volume ultrafiltration using a super high flux filter achieved cytokine clearances comparable to, or greater than, those currently achieved for urea during standard continuous renal replacement therapy.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                July 2003
                17 November 2004
                : 94
                : 3
                : c75-c80
                Departments of aNephrology, bAnesthesiology, and cCardiology, Charité, Humboldt University of Berlin, Berlin, and dGambro Corporate Research, Hechingen, Germany
                72024 Nephron Clin Pract 2003;94:c75–c80
                © 2003 S. Karger AG, Basel

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