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      The immunological effects of continuous veno-venous haemodiafiltration in critically ill patients

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          Abstract

          Background:

          Haemodynamic instability is common in septic patients with acute renal failure. Continuous veno-venous haemodiafiltration (CVVHD) is therefore used as an alternative to conventional haemodialysis. Haemodialysis is associated with an activation of the immune system. The aim of the present study was to test the hypothesis that initiation of CVVHD influences the immune system with release of proinflammatory cytokines followed by a decrease in granulocyte activation, as assessed by the expression of adhesion molecules.

          Results:

          Fifteen patients were included. Mean Acute Physiology and Chronic Health Evaluation-2 score before CVVHD was 19 (range 8⌓27). Mean duration of CVVHD treatment was 9 days (1⌓21 days). Tumour necrosis factor-α and interleukin-8 were detectable in plasma in all patients, whereas interleukin-10 was detectable only in a few patients. Proinflammatory and anti-inflammatory cytokines were detected in the ultrafiltrate. Large intraindividual and interindividual variations were demonstrated for all of the immunological parameters studied.

          Conclusion:

          The hypothesis that CVVHD induces the release of proinflammatory cytokines followed by a decrease in granulocyte activation was not confirmed in the present study. The heterogeneous group of patients studied, with different underlying diseases and various durations of illness before the start of CVVHD, might have contributed to the difficulty in demonstrating the proposed immunological effect of CVVHD.

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          Most cited references19

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          Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome.

          To compare two forms of continuous renal replacement therapy, continuous venovenous hemofiltration (CVVH) vs. continuous venovenous hemodialysis (CVVHD), in terms of the removal of inflammatory mediators from the blood of patients with systemic inflammatory response syndrome and acute renal failure. Randomized crossover, clinical study. University teaching hospital. Thirteen patients with systemic inflammatory response syndrome and acute renal failure receiving continuous renal replacement therapy. Patients were randomized to receive either convective clearance using CVVH or diffusive clearance using CVVHD for the first 24 hrs, followed by the other modality for 24 hrs. All treatments utilized AN69 hemofilters. CVVH was performed with an ultrafiltration rate of 2 L/hr and CVVHD with a dialysis outflow rate of 2 L/hr. Plasma and ultrafiltrate concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and sL-selectin were measured at 0, 1, 3, 6, 12, and 24 hrs by radioimmunoassay. Plasma endotoxin concentrations were also measured at 0, 12, and 24 hrs by chromogenic assay. CVVH was associated with a 13% decrease in plasma TNF-alpha concentrations compared with a 23% increase while on CVVHD (p < .05). Mean plasma concentrations of IL-6, IL-10, and sL-selectin were unchanged over time and between therapies. Only minimal amounts of mediators were recovered in the effluents with either therapy except for IL-6. The clearances for IL-6 were different between therapies, 1.9+/-0.8 (SD) mL/min for CVVHD and 3.3+/-1.5 mL/min for CVVH, (p< .01). Plasma endotoxin concentrations were not different between therapies. CVVH resulted in a decrease in plasma TNF-alpha concentrations as compared with CVVHD, while the type of transport mechanism used did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. Differences in clearance for IL-6 between CVVH and CVVHD did not translate into significant changes in circulating IL-6 concentrations.
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            Plasma cortisol levels in patients with septic shock.

            To investigate the endogenous adrenocortical response to sepsis, plasma cortisol concentrations were measured in 37 patients (53 +/- 3 yr of age) with septic shock. Patients were studied 11 +/- 2 h after shock commenced. Vasopressor therapy was required in 35 of 37 patients (median dopamine infusion rate of 11 micrograms/kg.min, range 3 to 74). Plasma cortisol concentrations were increased markedly (median 50.7 micrograms/dl, range 15.6 to 400) above normal values (10 to 20 micrograms/dl) in patients with septic shock. Neither patients who reversed their shock nor those who survived to hospital discharge had significantly different plasma cortisol concentrations from those who did not. Patients with Gram-positive infections had increased cortisol levels compared with those who had Gram-negative infections (median 83 micrograms/dl, range 32 to 400 vs. median 44 micrograms/dl, range 16 to 81, respectively; p less than .05). The source of infection, amount of vasopressors infused, and severity of shock were not associated with differences in cortisol concentrations. The length of time in shock before collection of the blood sample for measurements of cortisol and mean arterial pressure at the time of blood collection had significant but weak negative correlations with cortisol concentrations (p less than .05, rs = .37 and p less than .05, rs = -.40, respectively). We conclude that plasma cortisol concentrations are increased in patients with septic shock, but that the degree of increase is variable. This variability may, in part, be related to type of infection, length of time in shock, and BP at the time of blood sampling.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Activation of complement by hemodialysis membranes: polyacrylonitrile binds more C3a than cuprophan.

              Conventionally, complement activation by hemodialysis membranes has been determined by measuring fluid phase C3a. Based on such measurements, polyacrylonitrile (PAN) membranes have been classified as weak activators compared to cuprophan. Previous studies have demonstrated, however, that PAN adsorb fluid phase C3a. Based on that observation, we hypothesized that complement activation by PAN might be artifactually underestimated if relatively large amounts of C3a remained membrane bound. In the present study, a method that allows the simultaneous quantification of both fluid phase and membrane bound C3a was used to assess complement activation by PAN and cuprophan. Pieces of membrane were incubated with C3-depleted serum that had been repleted with radiolabeled C3. Subsequently, the supernates and membranes were subjected to SDS-PAGE, and complement activation was quantified by determining the radioactivity of the C3a bands in the gel. The results showed that while the serum exposed to cuprophan membranes contained almost five times more C3a than that exposed to PAN, approximately 80 times more C3a was bound to the PAN membranes. Consequently, the total amount of C3a generated in the presence of PAN was higher than that generated in the presence of cuprophan. We conclude that assessment of complement activation by hemodialysis membranes using fluid phase C3a measurements alone may be misleading.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                1999
                11 November 1999
                : 3
                : 6
                : 159-165
                Affiliations
                [1 ]Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark.
                [2 ]Department of Clinical Biochemistry, Vejle Central Hospital, Vejle, Denmark.
                Article
                cc-3-6-159
                29032
                11056741
                1698dc1c-35cc-4dc9-9c12-eb790e6e0a26
                Copyright © 1999 Current Science Ltd
                History
                : 11 June 1999
                : 8 July 1999
                : 3 August 1999
                : 20 October 1999
                Categories
                Research Paper

                Emergency medicine & Trauma
                acute renal failure,continuous veno-venous haemodiafiltration,critical illness,haemodiafiltration,immune system

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