Academic literature on the topic 'High-cut off hemofiltration'

Objective To test the hypothesis that hemofiltration using a new large pore cellulose triacetate hemofilter can achieve effective ultrafiltration of cytokines. Design Ex-vivo study. Setting Laboratory of Intensive Care Unit in tertiary hospital. Subjects Six healthy volunteers. Interventions Blood from 6 volunteers was incubated for 4 hours with 1 mg of endotoxin and then circulated through a closed hemofiltration circuit with a large pore cellulose triacetate hemofilter (nominal cut-off point: 60 kilodaltons). Hemofiltration was conducted at 1 L/h or 6 L/h of ultrafiltrate (UF) flow at the start of extra-corporeal circulation, and after 2 and 4 hours. Samples were taken from the arterial, venous and UF sampling ports. Measurements and main Results IL-Iβ, IL-6, IL-8, IL-10, TNFα, and albumin were measured. Sieving coefficients (SC) above 0.6 were achieved for IL-Iβ and IL-6 and SCs above 0.3 were achieved for IL-8 and TNF-α at 1 L/h. Sieving coefficients of all cytokines (except IL-10, p=0.22) were reduced when the ultrafiltration rate was increased from IL/h to 6 L/h (p<0.01), but the increase in ultrafiltration rate resulted in an overall increase in the clearance of all cytokines (p<0.001). The highest SC for albumin was 0.07 at 4 hours at 1 L/h, and fell to 0.01 at 6 L/h. The SCs for IL-8 fell at 4 hours (p<0.01), but the SCs for other cytokines did not change. No adsorption of cytokines and albumin was observed. Conclusion High volume hemofiltration (HVHF) using a new large pore cellulose triacetate filter achieved cytokine clearances greater than those reported with currently available hemofilters.

Extracorporeal blood purification techniques have emerged and evolved in the recent years as a potential therapy for the purpose of immunomodulation in acute conditions like sepsis. Understanding the extent of immune system dysregulation involved in the pathophysiology of these conditions, resulted in the development of such treatment strategies aiming at restoring a balanced inflammatory response. Beyond conventional continuous renal replacement therapy, high volume hemofiltration, high cut-off membranes, adsorption alone and coupled plasma filtration adsorption are well-described techniques in the literature. The evidence to support their routine use, however, is conflicting and insufficient at this stage. Despite the low-quality level of evidence in favor of utilizing these techniques, studies to further explore their effectiveness, safety, and potential novel applications, continue to evolve. Our review aims at focusing on adsorption therapy, particularly using the adsorption columns Cystosorb.

Cardiovascular complications are a leading cause of morbidity and mortality in dialysis patients. Cardiovascular mortality is more than 40% of the total mortality in this cohort of patients. Recently, there has been an increase in publications on the role of uremic toxins, including “middle molecules”, in the development and progression of cardiovascular complications in dialysis patients. Conventional low-flux (LF) hemodialysis well removes small molecular weight uremic toxins not bound with protein. Evidence for the role of "middle molecules" in the development of many complications, including cardiovascular complications, has contributed to the emergence and development of such dialysis therapy methods as high-flux (HF) hemodialysis, hemofiltration (HF) and hemodiafiltration (HDF). Further evolution of membrane technology has led to the development of protein-leaking membranes or super-flux or high cutoff (HCO) membranes. These membranes are capable of removing molecules in excess of the molecular weight of albumin. The use of these membranes is limited because of the risk of hypoalbuminemia. Today, the closest approximation to the natural glomerular membrane is the so-called Middle Cut-Off (MCO) membrane. The use of MSO membranes is implemented in a new method of dialysis therapy - expanded hemodialysis (HDx). The method is defined as a treatment where diffusion and convection are conveniently combined inside a hollow-fibre dialyser equipped with an MCO membrane. A standard hemodialysis machine is used for the HDx. Increased removal of large medium molecules in HDx may lead to an improvement of clinical outcomes, including a decrease of the cardiovascular events incidence, an all-cause and cardiovascular mortality reduction in dialysis patients.

Abstract Abstract 4186 We report the case of a thalassemic patient with asymptomatic malaria in which the infection became clinically manifest only after blood transfusion, mimicking a febrile non haemolytic transfusion reaction. The patient was a 19 yr old thalassemic girl from Togo regularly and uneventfully transfused every 60-90 days since the age of 5 months and splenectomised at 13 yrs. Two malaria episodes in 1995 and 1997 were treated with quinine and halofantrin respectively. In February 2008 the transfusion interval shortened (15 days) and blood transfusions were constantly followed after 30-40 hours by high fever (39-4028C) and hypotension. The patient was referred to our Hospital to clarify and overcome the transfusion problems. Malaria attacks were excluded by the referring clinic. At admission, Hb was 5.9 g/dL, Hct 18.3%, MCV 71.8 fL, MCH 23.1 pg, MCHC 32.2%, reticulocytes 0.82%. WBC 13.1 × 109/L platelet count 953 × 109/L erythroblasts 12.7% of nucleated cells. Molecular analysis of β and α genes revealed double heterozygosity for β IVS1-1 G>A and β IVS2-849 A>G, associated with deletion 3.7 (-α3.7) at the heterozygous state. G6PD 6.29 IU/g Hb (ref.values 5.97±1), Pyruvate kinase 25.1 IU/gHb (ref. v. 11.9-16.1). Red cell osmotic fragility was decreased. The cytofluorimetric analysis of red cells labelled with eosin 5 maleimide gave normal results. Direct antiglobulin test was negative and red cell alloantibodies were not detected. The patient's blood group assessed by molecular biology testing was: genotype O1A2, phenotype A2; ccDee; K-k+; Jk(a+b-); Fy(a-b+); M+N+S+s-. The patient was given 2 crossmatch negative, filtered O neg units: the post-transfusion Hb values were 9.9 g/dL. Thirty-two hours later the patient developed fever (40°C) and hypotension followed by disseminated intravascular coagulation, metabolic acidosis and anuria. Direct and indirect antiglobulin tests were negative on a post-transfusion sample. Because of the rapid worsening of clinical conditions she was admitted to the Intensive Care Unit of our Hospital. Septic shock was excluded on the basis of negative blood cultures and infectious diseases testing. Microscopic examination of thick blood smear was negative for malaria parasites on 2 consecutive days and the malaria rapid diagnostic test (RDT) (Core Malaria Pan-PV-PF®, Core Diagnostics, U.K.-Effegiemme, Nerviano, Milano, Italy) gave inconsistent results. Anti Plasmodium total antibodies (Malaria EIA New Market Laboratories U.K.- Bio-Rad Italia) were detected in the serum at high levels (odd sample/cut off 22). Vital functions were supported by mechanical ventilation, amine administration and continuous venous-venous hemofiltration (CVVH). Broad spectrum antibiotic therapy was started. Fresh frozen plasma and two units of PRC were transfused on day 1 and 2 without increment of Hb level. Three days later, the examination of the peripheral blood smear for counting schistocytes revealed the presence of parasites in a very small number of red cells. This finding was almost simultaneous to the availability of PCR testing results that were positive for P. Falciparum. The differential agglutination with anti A antibody performed on a blood sample collected at admission to ICU allowed to separate patient's and donors' red cell. Counting the number of parasitized red cells in total blood and in the donor fraction blood revealed that the parasitized cells were almost exclusively those of donors (14.4 % vs 0.029%). Treatment with quinine chlorhydrate 500 mg i.v. every 8 hr for 3 days followed by oral quinine sulphate 500 mg every 8 hr for 3 days was successfully undertaken without significant side effects leading to dramatic improvement of clinical conditions and to eradication of P. falciparum. Two RBC units were effectively transfused without any reaction, and in the following two weeks the patient maintained stable haemoglobin values. After discharge, the transfusion interval returned to the previous values (60-90 days) without any post-transfusion reaction. We therefore think that the transfusion of normal, non malaria-resistant red cells fuelled the P. falciparum infection causing fever, DIC and acidosis giving rise to a very severe, atypical febrile non haemolytic transfusion related reaction. Disclosures: No relevant conflicts of interest to declare.

Abstract Background and Aims Acute kidney injury (AKI) is frequent among critically ill patients and it is associated with high mortality. Rhabdomyolysis is a distinct cause of AKI. As myoglobin has renal toxic effects, clearance via continuous renal replacement therapy (CRRT) may be favourable. Current international guidelines recommend regional citrate anticoagulation (RCA). Clinical data comparing different modalities of CRRT addressing myoglobin clearance are lacking. Hemofiltration is recommended to eliminate myoglobin, which requires systemic anticoagulation. RCA would be impractical due to the high citrate load as a result of the higher blood flow. Continuous veno-venous hemodiafiltration (CVVHDF) is one opportunity to realize lower citrate load and maintain middle molecule clearance. Another approach may be the application of hemodialysis with high cut-off (HCO) membranes with a pore size larger than 0.01 μm in CVVHD (CVVHD-HCO). We have previously shown that CVVHD-HCO is superior to conventional high-flux dialyser regarding the clearance of β2-microglobulin. Based on this finding, we analyzed of various etiologiesre Filter lilifespan mit dem efonnummer der Virologie zum Befunderfragenmyoglobin clearance with CVVHDF compared to CVVHD-HCO with RCA. Method The present study is a prospective, randomized, single-blinded, monocentric trial. We enrolled patients from May 2017 to September 2018 in our 28-bed medical ICU at the University Hospital Leipzig. We screened 430 patients with AKI and indication for RRT for eligibility. A total of 70 patients underwent randomisation 1:1 into the intervention (CVVHD-HCO, high cut-off dialyzer Ultraflux EMiC2) and control group (CVVHDF, high-flux dialyzer Ultraflux AV1000S). The concentrations of myoglobin (17053 Dalton (Da), urea (60 Da), creatinine (113 Da), β2-microglobulin 11800 Da), interleukin 6 (IL-6, 26000 Da) and albumin (66470 Da) were measured before (pre) and after (post) the dialyzer 1, 6, 12, 24 and 48 h after initiating CRRT. We hypothesized non-inferiority of CVVHD-HCO versus CVVHDF regarding myoglobin clearance (primary end-point). Results Myoglobin clearance showed non-inferiority in the intervention group for all time points. The dialyzer in the intervention group resulted in even a better myoglobin clearance during the whole study period. (Table 1). Clearance values for urea and creatinine were equal and there was no albumin loss in both groups.β2-microglobulin clearance was significantly better in the intervention group than in the control group at all time points. The clearance of IL-6 was also better at T0 in the intervention group. The filter lifespan was 51.5 hours (CI: 44.24; 58.76) in the control group and 62.3 hours (CI 56.83; 67.7) in the intervention group (log-rank, p=0,029). Conclusion Myoglobin can be reliably cleared using both CVVHD-HCO and CVVHDF. Nevertheless, the plasma specific clearance rate of myoglobin was higher with CVVHD-HCO. High myoglobin levels are associated with AKI and higher mortality rates and on this account clearance of myoglobin represents a relevant clinical issue.

Zirkulierende inflammatorische Mediatoren spielen eine zentrale Rolle in der Induktion und Unterhaltung eines septischen Multiorganversagens (MOV). Tritt im Rahmen eines septischen MOV ein akutes Nierenversagen auf, so wird der Einsatz einer Nierenersatztherapie notwendig. Kontinuierliche Nierenersatztherapieverfahren (CRRT) haben sich hier bewährt. Der Einsatz von CRRT zur adjuvanten Therapie des septischen MOV ist in den neunziger Jahren aufgekommen. Grundlage bildet die Hypothese, dass durch die Reduktion von Spitzenpegeln pro- and anti-inflammatorischer Mediatoren im Blutplasma die Homöostase der Immunabwehr wiederhergestellt werden kann. Kommerziell erhältlichen Hämofilter weisen aufgrund ihrer Konstruktion nur eine geringe Clearanceleistung für inflammatorische Mediatoren auf. In Kooperation mit der Industrie (Gambro, Medical Research, Hechingen, Germany) entwickelten wir einen neuartigen, großporigen Hämofilter für den klinischen Einsatz. Der Hämofilter wurde konzipiert, um Moleküle in einer Größe von bis zu 60 kD aus dem Blut septischer Patienten zu eliminieren. In einer ersten Pilotstudie wurde der Hämofilter auf seine klinische Verwendbarkeit untersucht. Untersucht wurde die hämodynamische Verträglichkeit, der Verlust an Bluteiweißen und Gerinnungsfaktoren sowie die Effektivität der Mediatorelimination am Beispiel von Interleukin-6 (IL-6) und Tumornekrosefaktor-alpha (TNF-alpha). Wir konnten zeigen, dass die großporige Hämofiltrationstherapie ein sicheres und effizientes Nierenersatzverfahren darstellt. Es erwies sich als hämodynamisch verträglich. Der kumulative Eiweißverlust lag bei 8 g/Tag. Signifikante Verluste an essentiellen Gerinnungsfaktoren wurden nicht beobachtet. Es zeigte sich zudem eine signifikante Filtration von im Blut zirkulierendem IL-6. Die Clearancekapazität für TNF-alpha war jedoch gering. In Folgestudien konnten wir zeigen, dass die großporige Hämofiltration immunmodulatorische Eigenschaften ausübt. Sowohl die Phagozytose-Aktivität zirkulierender polymorphkerniger Leukozyten und Monozyten, als auch die Proliferationseigenschaften von T-Lymphozyten wurden günstig beeinflusst. Um den Verlust an Bluteiweißen durch den großporigen Hämofilter zu reduzieren, wurden verschiedene Nierenersatzstrategien experimentiert. Der diffusive Stofftransport scheint dem konvektiven Verfahren hinsichtlich der Mediatorelimination, bei deutlich günstigerem Effekt auf den Proteinhaushalt, gleichwertig zu sein. In wieweit die großporige Hämofiltration den Krankheitsverlauf septischer Patienten beeinflussen kann, ist Gegenstand aktueller Studien.
Inflammatory mediators play a pivotal role in the induction and maintenance of a septic syndrome. In the course of a septic multiorgan dysfunction syndrome, acute renal failure (ARF) often necessitates the use of renal replacement therapy. Continuous renal replacement therapy (CRRT) is the treatment of choice in this regard, and convection (hemofiltration) has become the most common used purification technique. Apart from representing a valuable renal replacement modality, CRRT also allows the elimination of inflammatory mediators. Since the early nineties CRRT has been used as an adjuvant treatment strategy in the septic multiorgan failure syndrome. It has been hypothesized that CRRT may re-institute the immunologic and hemostasilogic homeostasis by reducing the peak cytokine concentration in circulating blood. Commercially available hemofilters do not allow for a substantial elimination of inflammatory mediators. Their clearance capacity for septic mediators is poor. In cooperation with an industry company (Gambro, Medical Research, Hechingen, Germany), we developed a high cut-off hemofilter for clinical use in septic patients. The hemofilter was developed in order to allow the elimination of septic mediators in the molecular weight range up to 60 kilodaltons (kD). In a first pilot study the newly developed hemofilter was analyzed for clinical feasibility. We studied the hemodynamic impact, the transmembrane loss of plasma proteins and coagulation parameters as well as the efficacy in regard to mediator elimination. For mediator elimination Interleukin-6 (IL-6) and tumor-necrosis-factor-alpha (TNF-alpha) were chosen. We were able to show, that high cut-off hemofiltration is a safe and effective renal replacement procedure. Hemodynamically high cut-off hemofiltration was well tolerated. The cumulative transmembrane total plasma protein loss was around 8g/day. Coagulation parameters were not effected. We further demonstrated, that high cut-off hemofiltration is able to significantly eliminate substantial amounts of circulating IL-6. However, the elimination capacity for TNF-alpha was poor. We were also able to show, that high cut-off hemofiltration exerts immunomodulatory properties. The phagocytotic activity of polymorphnuclear leukocytes and monocytes as well as proliferative capacity of lymphocytes were positively influenced. In order to reduced transmembrane protein losses through the high cut-off hemofilter, a variety of different renal replacement strategies were tested. Diffusive purification techniques were comparable to convective techniques in regard to the mediator elimination capacity, but were associated with significantly lower transmembrane protein losses. Whether high cut-off hemofiltration can positively influence the course of critically ill septic patients is still under investigation.