Coupled Plasma Filtration And Adsorption Research Articles

Hemoperfusion in anesthesia and intensive care medicine: benefits, risks, and evidence for different systems

Hemoperfusion is atechnique for the extracorporeal elimination of endogenous and exogenous toxins and harmful mediators by adsorption. It can be used as astand-alone device, as part of aheart-lung machine or extracorporeal membrane oxygenation (ECMO) or, as is currently the case, integrated into akidney replacement procedure. In the meantime, various suppliers offer devices with different technologies. The aim of this work was to evaluate the benefits, risks and evidence of the different systems, how they work and for which indications they are approved in Germany. To achieve this goal, anarrative assessment of the existing literature and guidelines for different indications was performed. The focus was on in vivo studies. In principle, adistinction must be made in adsorption techniques between pure adsorption and the combination as adsorption and kidney replacement therapy. The adsorbers available in Germany include Cytosorb®, HA-330, Seraph®-100 and Toraymyxin. Combined procedures (adsorption and kidney replacement) are offered with coupled plasma filtration and adsorption (CPFA) and oXiris®. Most adsorbers have been developed for cytokine and endotoxin removal in patients with sepsis; however, to date, no randomized controlled trial (RCT) has demonstrated asurvival benefit when using hemoperfusion. Therefore, the S3 guidelines for treatment of sepsis and the surviving sepsis campaign guidelines advise against its routine use. When the corona pandemic began, hemoperfusion was considered as apromising therapeutic approach. Cytosorb®, Seraph®-100, and oXiris® received emergency approval by the FDA to be used in critically ill patients with COVID-19, so questions arose about the appropriateness and importance of its use; however, the data generated did not show positive results, so its use cannot be recommended routinely either. In addition, they are not mentioned as atreatment option in the current guidelines. The use of adsorption procedures in patients with liver failure and rhabdomyolysis has only been rudimentarily studied, so any evidence is currently lacking. The only adsorber that has CE approval in Germany for both applications is Cytosorb®. In the next few years, studies will have to follow that investigate the efficacy and thus either justify or refute the use in clinical routine. Hemoperfusion procedures are used in the heart-lung machine as part of cardiac surgery for either cytokine or anticoagulant adsorption. No congruent data are available to support the use for the elimination of cytokines. If emergency cardiac surgery is required in apatient with pre-existing anticoagulation, hemoperfusion procedures can be used to prevent bleeding complications. Cytosorb® has CE approval for this indication. All available techniques are nonselective adsorption processes, so that adsorption of known and unknown substances can occur. Unintentional adsorption of drugs, such as various anti-infective agents is arelevant risk, especially when used in patients with sepsis. Various adsorption systems can eliminate different known and unknown substances. Currently, there is alack of evidence for all indications and systems to justify their routine use except in clinical trials. Future clinical trials should evaluate the potential benefits but also dangers, so that in the meantime the routine use can be justified or arecommendation against the use can be given.

LPS removal reduces CD80-mediated albuminuria in critically ill patients with Gram-negative sepsis.

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care ( n = 35) or not ( n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Influence of Timing of Initiation and Volume of Processed Plasma on the Outcome of Septic Shock Patients Treated with Coupled Plasma Filtration and Adsorption

Background: The extracorporeal removal of mediators is a rescue strategy for septic shock patients, which is still under investigation. Several techniques are available: coupled plasma filtration and adsorption (CPFA) combines plasma processing with renal replacement therapy. Methods: The study aimed to elucidate the role of both timing of initiation and intensity of treatment on the outcome, for which we retrospectively studied 52 patients. We collected the overall pre-CPFA time interval, starting from the first episode of hypotension in the wards and the volume of processed plasma (Vp), which we used as a proxy for intensity of treatment. Results: Timing of initiation did not significantly differ between survivors and non-survivors (25 vs. 27 h), while the Vp did (0.25 vs. 0.17 L/kg/session, p < 0.05). The significance of Vp was confirmed by a multiple logistic regression model. Conclusion: Our study confirms that intensity of CPFA, but not its timing of initiation, correlates with survival of septic shock patients.

The Hematocrit Affects the Volume of Plasma Treated With Coupled Plasma Filtration and Adsorption With Predilution.

Coupled plasma filtration and adsorption (CPFA) is an extracorporeal blood purification technique proposed for the treatment of septic-shock. By removing pro- and anti-inflammatory mediators from plasma, CPFA is supposed to have a therapeutic effect on the abnormal inflammatory response seen in this condition. Recently, blood predilution with citrate solution has been adopted to prevent clotting in the CPFA circuit-one of the main problems of the technique. Taking into account the patient's hematocrit, we worked out a formula for the volume of plasma effectively treated by CPFA after predilution. Neglecting this effect, as is commonly done, introduces significant distortions in the estimation of the volume, possibly causing under-treatment. The distortion is stronger when the hematocrit and the predilution fraction are large and weaker when both values shrink. By correctly indicating the daily dose of plasma adsorption received by patients, this formula is essential for assessing the therapeutic efficacy of CPFA and, subsequently, establishing its optimal doses.

REDUCING THE SEVERITY OF RENAL GRAFT ISCHEMIC AND REPERFUSION INJURY WITH COUPLED PLASMA FILTRATION AND ADSORPTION

Aim: to evaluate the effectiveness of coupled plasma filtration and adsorption (CPFA) in reducing the severity of the renal graft ischemic and reperfusion injury. Materials and methods: shortand long-term results of renal transplantation in 33 pairs of recipients were analyzed. The patients were divided into two groups: in 33 recipients of the study group we performed CPFA in the early postoperative period. In the comparison group in 33 recipients with paired grafts CPFA was not performed. Results. The proportion of patients with good initial and delayed graft functions in the two groups was the same. In patients with delayed graft function from the study group a significantly greater rate of creatinine and urea decrease and glomerular filtration rate (GFR) increase than in patients of the comparison group were observed. Among patients with good initial graft function the differences between the groups were not significant. We have also analyzed long-term results of the transplantations: patients who received CPFA in the early postoperative period had lower levels of creatinine, urea and daily proteinuria and higher GFR in 1 year time. Thus, as a result of CPFA in the early postoperative period the improvement of graft function and graft survival prognosis can be expected in the long-term.

COUPLED PLASMAFILTRATION AND ADSORPTION IN SEPTIC COMPLICATIONS IN RENAL TRANSPLANT RECIPIENTS

In the article fi rst experience with the usage of coupled plasma fi ltration and adsorption in the treatment of sepsis in patients after kidney transplantation has been presented. Aim: to make a comparative assessment of the impact of hemo fi ltration and coupled plasma fi ltration and adsorption (CPFA) on systemic hemodynamics and alveolar-capillary diffusion, as well as the dynamics of the pro- and antiin fl ammatory cytokines in patients with sepsis after renal transplantation. Methods and results. The study included 24 recipients. In the main group (n = 14), we used a combination of CPFA and hemo fi ltration. The patients of the comparison group (n = 10) we used an isolated hemo fi ltration. In patients of both groups we observed improvement of hemodynamics and lung function. In doing so by the fi fth day after the second procedure in patients of the main group the results were signi fi cantly better. This effect we mainly associate with a reduction in the activity of the systemic in fl ammatory response and the rate of progression of sepsis. This is con fi rmed by the fact that circulating pro- and anti-in fl ammatory cytokines were expressly removed during the CPFA. Conclusion. As a result of the CPFA and the hemo fi ltration we observed an increase in mean arterial blood pres- sure, improving gas exchange in the lungs, as well as reducing the need for vasopressor support. In this case, the additional sorption removal of circulating in fl ammatory mediators reduces the activity of the systemic in fl am- matory response, which can signi fi cantly increase the effectiveness of the therapy.

Effects of the Volume of Processed Plasma on the Outcome, Arterial Pressure and Blood Procalcitonin Levels in Patients with Severe Sepsis and Septic Shock Treated with Coupled Plasma Filtration and Adsorption

Aims: To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage. Methods: Patients with severe sepsis and septic shock with ≥2 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit. Results: Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors. Conclusion: These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensity.

Different effect of CVVHDF and coupled plasma filtration and adsorption on IL-6 and procalcitonin in sepsis

A decrease of IL-6 and procalcitonin (PCT) correlates with survival during sepsis [1]. Coupled plasma filtration and adsorption (CPFA) supports the renal function and removes proinflammatory mediators, but few clinical studies compare the effects of CPFA and CVVHDF, the standard of care in septic patients with renal failure [2]. The aim of this study is to evaluate whether CPFA and CVVHD have a different effect on IL-6 and PCT in septic patients.

Coupled plasma filtration and adsorption in septic shock: a multicentric experience

Introduction Recently extracorporeal removal of mediators and endotoxins improved haemodynamics, organ dysfunction and mortality in patients with abdominal sepsis [1]. Coupled plasma filtration and adsorption (CPFA), too, may improve haemodynamics, respiratory function and mortality through removal of proinfl ammatory mediator. The aim of this multicentric study is to evaluate the haemodynamic response and the respiratory function, and to evaluate the reduction of infl ammatory markers during CPFA.Methods Fifty-fi ve septic patients were enrolled in this study. Every patient had four CPFA treatments (LINDA; Bellco-Mirandola, Italy) for 8 hours with Qb = 200 ml/minute, Qultrafi ltration = 30 ml/kg/hour and Qplasma = 20% of Q b. At T0 (basal), T1 (after fi rst cycle), T2 (after second cycle), T3 (after third cycle)and T4 (after fourth cycle) we evaluated haemodynamic parameters, norepinephrine dosage, PaO2/FiO 2 ratio, plasma IL-6, and procalcitonin (PCT). The ANOVA test was used to compare changes during times study. P <0.05 was considered statistically significant. Results Patients enrolled in the study have been submitted to 256 CPFA treatments for 2,650 hours. Table 1 presents the main results of the study. IV quartile of IL-6 is shown in Table 1Conclusions In this large multicentric study, CPFA may improve haemodynamic status and respiratory function. Plasma fi ltration and adsorption of proinfl ammatory mediators may explain this improvement. Larger randomized controlled trials are indicated to confi rm these data. Reference 1.Cruz D, et al.: JAMA 2009, 23:2445-2452.

It's the end of the world as we know it - An era comes to a close

in the year 2008 (1). In this timeframe, much work has been done to pursue new strategies to enhance quality and scientific ranking of the “Blue Journal”. In this edito-rial, we will provide a short update on some outcomes of our activity in the last year and a half, and a few thoughts about the new structure of the Blue Journal in 2010.As anticipated in the December 2008 editorial, a key point in our strategy was to consolidate the legacy of the Blue Journal, in terms of its European character and mis-sion, to broaden it up, and integrate it with the require-ments presented by the world situation and advance-ments in science.The analysis reported in the press of the new world economy and demography suggests that countries that once were considered emerging economies in the East and Far East have now become established industrial powers. Over the last few years, in these countries major financial investments have been made in these regions (and are still being made) in education and science to pro-mote the development of the country. Since we started serving as Editors of the Blue Journal, efforts have been made to attract more quality submissions and involve in the editorial activities of the Blue Journal more scien-tists from the Middle East, East and Far East countries. Scientists from China have responded with the greatest enthusiasm, and have contributed a significant number of papers to the Blue Journal in the last year and a half. Analysis of these papers shows the quality of research in China, and how Chinese research in the field of substitu-tive medicine in that country spans the spectrum from traditional to very innovative topics.As is traditional in the Blue Journal, a consistent number of published papers focused on how to exploit the thera-peutic use of extracorporeal blood treatment processes and minimize the harm to patients caused by incidents to the vascular access. Tao et al (2) and Yu et al (3) reported on the improvement of monocyte function and the res-toration of immune homeostasis during the veno-venous hemofiltration treatment of severe pancreatitis in a por-cine pancreatitis model or in patients, respectively. The improvement was more significant in non-septic patients in the early phase of the disease. Mao et al (4) reported on the results of a prospective, pilot study on the effects of coupled plasma filtration and adsorption (CPFA), as com-pared to high volume hemofiltration (HVHF), on the im-mune function of patients with multiple organ dysfunction syndrome. They showed that CPFA increases the anti-in-flammatory to pro-inflammatory mediators ratio, improves antigen presentation ability, and restores leukocyte re-sponsiveness to a larger extent than HVHF. A silent, but potentially hazardous complication of catheter fracture in a totally implantable venous access port was reported by Wang et al (5). After a saline flush, the subcutaneous tis-sue around the port presented a painful, rapid swelling. A chest CT scan showed that the catheter had fractured, and that a fragment had migrated and was embolized into the right hepatic vein. Percutaneous transfemoral retrieval of the catheter fragment under fluoroscopic guidance was successfully performed and avoided more serious com-