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As highlighted by the last international consensus definition for sepsis and septic shock (sepsis-3), sepsis comes from a complex relationship between a pathogen and a dysregulated host response. To date, the treatment of sepsis is based on antimicrobial treatment, source control, and organ support. Extracorporeal blood purification therapies have been proposed as adjuvant therapies to modulate the dysregulated inflammatory response. These therapies aim mostly at removing inflammatory mediators (cytokines) and endotoxins from the blood. However, so far, they failed to clearly demonstrate an improvement in patient survival when evaluated in randomized trials. Recently, new devices directly targeting the primary determinants of sepsis, e.g., the pathogen itself and the host immune cells, have been developed. This short review aimed at presenting new blood purification devices that have recently been developed to target pathogens and immune cells. For each, we will present the mechanism of action of the therapy and discuss the related literature., (© 2022 S. Karger AG, Basel.)

Sepsis is the primary cause of acute kidney injury in critically ill patients. During the past decades, several extracorporeal blood purification techniques have been developed for sepsis and sepsis-induced acute kidney injury management. These therapies could act on both the infectious agent itself and the host immune response. In this article, we review the available literature discussing the different extracorporeal blood purification techniques, including high-volume hemofiltration, cascade hemofiltration, hemoperfusion, coupled plasma filtration adsorption, plasma exchange, and specific optimized renal replacement therapy membranes., (Copyright © 2019. Published by Elsevier Inc.)

Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known to induce organ dysfunctions. Different therapies have been developed to address certain steps of the immune dysregulation. Most of the available blood purification devices focus on a single target, such as the endotoxin that triggers the immune cascade, or the cytokine storm that causes organ damages. However, the highly adsorptive membrane named oXiris® is a unique 4-in-1 device that combines cytokine and endotoxin removal properties, renal replacement function, and antithrombogenic properties. More recently, promising treatments that focus on the pathogen itself or the immune cells have been developed and are currently under investigation. In this review, we aim to summarize, according to their target, the different extracorporeal blood purification techniques that are already available for use. We will also briefly introduce the most recent techniques that are still under development. Because of its unique ability to remove both endotoxins and cytokines, we will particularly discuss the highly adsorptive preheparinized oXiris® membrane. We will present its properties, advantages, pitfalls, as well as therapeutic perspectives based on experimental and clinical data. Video Journal Club "Cappuccino with Claudio Ronco" at  https://www.karger.com/Journal/ArticleNews/223997?sponsor=52., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Background: Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT)., Summary: Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74-87] SAPS II quartile and 70 vs. 98% for the [87-163] SAPS II quartile, p < 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52-2.45] µg/kg/min; at 48 h it was 0.20 [0.09-1.14] µg/kg/min, p = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. Key Messages: CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections., (© 2019 The Author(s). Published by S. Karger AG, Basel.)

Coupled plasma filtration adsorption (CPFA) is a blood purification therapy aimed at modulating the host inflammatory response involved in sepsis pathogenesis. One potential drawback of this technique is the unexpected elimination of antibiotics. The aim of this study was to assess the elimination of several antibiotics with CPFA. We performed a retrospective analysis of the serum and ultrafiltrate concentrations of different antibiotics routinely measured during CPFA sessions in five patients experiencing septic shock. The adsorbent extraction ratio (AER) for piperacillin and vancomycin 2 h into the CPFA session were high: 95.4 ± 6.9% and 99.6 ± 0.9%, respectively. These AER decreased significantly by 8 h (at 8 h: 6.3 ± 51.8% and -30.2 ± 25.6%, respectively), suggesting saturation of the resin cartridge. Conversely, the tazobactam AER was low (7.2 ± 15% after 2 h of CPFA). No significant changes in the mean serum concentrations of piperacillin, tazobactam, and vancomycin were observed. Thus, as opposed to tazobactam, we report high adsorption of piperacillin and vancomycin on the CPFA resin but with no reduction in serum concentrations.

Background: Unlike pharmacologic interventions in sepsis, extracorporeal blood purification, which is widely used in septic patients, is not typically studied in experimental rodents. Most of the previous studies have performed extracorporeal blood purification in larger animals and typically use arteriovenous (AV) vascular access. We developed a venovenous (VV) purification model in the rat as an adjunct for the treatment of sepsis., Methods: Using adult male Sprague-Dawley rats, we cannulated the femoral artery or vein and the jugular vein with P50 tubing and created an AV or VV circuit. Blood flow was maintained by arterial pressure in the AV circuit, whereas in the VV circuit the blood flow was regulated using a rotary pump. The safety of this circuit was evaluated using the changes of blood interleukin 6, rectal temperature, and 7-d survival with sham extracorporeal circulation (circuit connection without treatment) compared with the control (without circuit). The main side complications of this VV circuit were compared with those of the AV circuit., Results: The differences in interleukin 6, body temperature, and cumulative survival were not statistically significant after extracorporeal circulation. The main complications of extracorporeal circulation occurred less often with VV compared with AV therapy: massive bleeding (2.5% versus 15%, P = 0.04); clot formation (2.5% versus 15%, P = 0.04). This VV circuit has been successfully used in different septic rodent models with different techniques (hemoadsorption and hemofiltration)., Conclusions: VV blood purification in a rodent model appears to be effective and is safer than AV circuit., (Copyright © 2013 Elsevier Inc. All rights reserved.)

High-volume hemofiltration is an extracorporeal therapy that has been available in the intensive care unit for more than 10 yr. Recent improvements in technology have made its clinical application easier and safer. However, the definition, indications, and management of this technique are still unclear, and considerable controversy and confusion remain. The aim of this review is to analyze the available data while taking into account the distinction between two very different clinical situations: acute kidney injury requiring renal support, and severe inflammatory states where blood purification has been suggested as an adjuvant therapy. For patients with acute kidney injury requiring renal replacement therapy, the two largest multicenter studies performed to date established that high ultrafiltration flow rates are not necessary. Conversely, much experimental and some clinical evidence suggest that high-volume hemofiltration can be beneficial for the subset of critically ill patients with severe inflammatory states such as septic shock.

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.

Sepsis is the primary cause of death in the intensive care unit. Extracorporeal blood purification therapies have been proposed for patients with sepsis in order to improve outcomes since these therapies can alter the host inflammatory response by non-selective removal of inflammatory mediators or bacterial products or both. Recent technological progress has increased the number of techniques available for blood purification and their performance. In this overview, we report on the latest advances in blood purification for sepsis and how they relate to current concepts of disease, and we review the current evidence for high-volume hemofiltration, cascade hemofiltration, hemoadsorption, coupled plasma filtration adsorption, high-adsorption hemofiltration, and high-cutoff hemofiltration/hemodialysis. Promising results have been reported with all of these blood purification therapies, showing that they are well tolerated, effective in clearing inflammatory mediators or bacterial toxins (or both) from the plasma, and efficacious for improvement of various physiologic outcomes (for example, hemodynamics and oxygenation). However, numerous questions, including the timing, duration, and frequency of these therapies in the clinical setting, remain unanswered. Large multicenter trials evaluating the ability of these therapies to improve clinical outcomes (that is, mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of blood purification in the management of sepsis.

Sepsis is one of the main causes of death in critically ill patients. The pathophysiology of sepsis is complex and not completely understood. The proinflammatory and anti-inflammatory response leads to cell and organ dysfunction and, in many cases, death. Thus, the goal of the intervention is to restore the homeostasis of circulating mediators rather than to inhibit selectively the proinflammatory or anti-inflammatory mediators. Blood purification has been reported to remove a wide array of inflammatory mediators. The effects are broad-spectrum and auto-regulating. Blood purification has also been demonstrated to restore immune function through improving antigen-presenting capability, adjusting leukocyte recruitment, oxidative burst and phagocytosis, and improving leukocyte responsiveness. A great deal of work has to be done in order to find and optimize the best extracorporeal blood purification therapy for sepsis. New devices specifically target the pathophysiological mechanisms involved in these conditions. High-volume hemofiltration, hemoadsorption, coupled plasma filtration adsorption, and high cutoff membrane are now being tested in septic patients. Preliminary data indicate the feasibility of these modified techniques in sepsis. Their impact on patient prognosis, however, still needs proof by large randomized clinical trials. Finally, the emerging paradigm of sepsis-induced immune suppression provides additional rationale for the development of extracorporeal blood purification therapy for sepsis., (2010 S. Karger AG, Basel.)

High-volume hemofiltration has been suggested as an adjuvant treatment of septic shock (renal support and immunomodulation of the host response via the removal of middle molecular weight molecules such as cytokines). Nevertheless, high-volume hemofiltration presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload. We describe cascade hemofiltration, a new high-volume hemofiltration system, which has been developed to limit these drawbacks by using a special extracorporeal circuit. Results of the first experimental study using this prototype are also reported. They demonstrate the technical feasibility, security and safety of the cascade system although other experimental and clinical studies are needed to continue evaluating this system.

Background: High-volume haemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock due to its capacities to remove from blood both pro- and anti-inflammatory mediators involved in the sepsis syndrome. Adsorption properties of some haemofiltration membranes are also interesting with this indication because inflammatory mediators are caught in the membrane itself. The aim of this study was to determine the haemodynamic and immunological effects of a new haemofiltration membrane, which has enhanced adsorption properties due to a special surface treatment, allowing the adsorption of endotoxins., Methods: We compared this membrane to a standard haemofiltration membrane both in vitro and in 20 sepsis-induced pigs, randomized in two groups. One group was haemofiltered with the treated membrane and the other with the standard haemofiltration membrane during 6-h HVHF sessions., Results: At the end of the experiment, mean +/- SD crystalloids requirements (5937 +/- 1588 versus 7587 +/- 1456 ml, P = 0.026), colloids requirements (1437 +/- 320 versus 1912 +/- 538 ml, P = 0.027), lactic acidosis (pH = 7.20 +/- 0.11 versus 7.10 +/- 0.07, P = 0.026) and pulmonary arterial hypertension (MPAP = 24 +/- 7 versus 34 +/- 8 mmHg, P = 0.008) were less pronounced when HVHF was performed with the treated membrane. In addition, mean +/- SD endotoxins levels were lower in the treated membrane group after 1 hour of HVHF (1.91 +/- 1.19 versus 11.07 +/- 10.64 EU/ml, P = 0.035). Cytokines levels were not different between groups except for IL-1beta, which was slightly lower in the treated membrane group., Conclusions: The use of a membrane with enhanced adsorption properties during a 6-h HVHF session in septic pigs improves haemodynamics compared to a standard haemofiltration membrane. These results are probably due to an efficient endotoxins and cytokines adsorption. A human study using this membrane is now necessary to confirm these results.

High-volume hemofiltration (HVHF) has been suggested as an adjuvant treatment of septic shock because of its capacities to remove inflammatory mediators from blood. Nevertheless, HVHF presents some important drawbacks, such as the depletion of low molecular weight molecules (nutriments, vitamins, trace elements and antibiotics) due to the high ultrafiltration rate, or the significant financial cost and nursing workload due to the frequent changes of large amounts of expensive sterile substitution fluids. A new hemofiltration system called "Cascade" has been developed, allowing very high ultrafiltration rates (120 mL/kg/h) limiting these drawbacks by using a special extracorporeal circuit. The objective of this study was to assess the technical feasibility of the Cascade system and to compare its hemodynamic impact to that of the standard HVHF system. Twenty sepsis-induced pigs were randomized in two groups: one group was hemofiltered with the standard HVHF system and the other with the Cascade system during a six-hour session. No technical problems were observed with the Cascade system during the experiment. At the end of the experiment, colloid requirements (989 +/- 355 mL vs. 1913 +/- 538 mL, P = 0.006), epinephrine requirements (0.82 +/- 0.42 mg vs. 3.27 +/- 3.02 mg, P < 0.001), lactic acidosis (pH = 7.33 +/- 0.08 vs. 7.10 +/- 0.07, P < 0.001) and mean pulmonary arterial pressure were less pronounced in the Cascade group. These results suggest that Cascade hemofiltration is technically feasible and safe. Moreover, compared with standard HVHF, it can reduce the severity of porcine septic shock.

Purpose: Septic shock is the leading cause of multiple organ failure and mortality in intensive care units. This condition seems to be related to an overproduction of both pro- and anti-inflammatory mediators, leading to an immunological dysfunction. Therapeutic strategies aimed at reducing blood and tissue concentrations of these mediators have been developed. One of these techniques, based on extra-renal filtration, is called "coupled plasma filtration and adsorption"., Source: English and French language articles published between 1984 and 2008 were identified through a computerized Medline search. Keywords and MeSH terms used were: "coupled plasmafiltration", "coupled plasma filtration", "adsorption", "blood purification", "cytokines", "hemofiltration", "sepsis". Relevant publications were retrieved and scanned for additional sources. Nine publications were found., Principal Findings: Coupled plasma filtration adsorption is an extra-corporeal treatment, based on non-specific cytokine adsorption on a specially designed resin cartridge, coupled with hemofiltration. Experimental studies and the first clinical trials have shown interesting results regarding hemodynamics and respiratory parameters. However, these trials failed to demonstrate any improvement in outcome., Conclusion: Additional evidence is needed to clarify the role of this blood purification technique for the treatment of septic shock.

Coupled plasma filtration adsorption (CPFA) is a new technology proposed for septic shock, removing both pro- and anti-inflammatory mediators. We report the first use of CPFA in France. The patient was 80-years-old and was admitted to the intensive care unit because of septic shock from urinary source. Besides conventional septic shock treatment, four successive CPFA sessions were daily performed and lasted from 6 to 11 hours. At the end of the sessions, a noteworthy hemodynamic and inflammatory improvement was observed. This case confirms the feasibility and the relative simplicity of CPFA. It also illustrates the recent and few scientific data of the medical literature concerning this technology.

Résumé Objectifs En cas d’épuration extrarénale continue (EERC), la thrombose des circuits engendre une perte de temps, une augmentation des coûts de traitement et des pertes sanguines pour le patient. L’objectif de cette étude est d’analyser l’impact d’un programme d’amélioration de la stabilité des séances d’EERC sur ces arrêts inopinés. Type d’étude Rétrospective et observationnelle. Patients et méthodes En janvier 2011, plusieurs changements ont été adoptés dans notre service pour la gestion de l’EERC, comprenant la mise en place de l’anticoagulation régionale au citrate, l’utilisation du mode hémodialyse continu avec membranes à point de coupure optimisé de type super high-flux et une formation des infirmiers de réanimation à la gestion des alarmes. Les séances d’EERC avant ces changements (années 2009 et 2010, groupe AVANT) et après (années 2011 et 2012, groupe APRÈS) ont été analysées. Le critère de jugement principal était l’incidence de ces arrêts imprévus. Une analyse de durée de vie des filtres a également été réalisée dans les deux groupes. Résultats Durant la période d’étude, 401 séances réalisées chez 152 patients ont été analysées. Des arrêts imprévus de séance sont survenus lors de 63 séances (40 %) dans le groupe AVANT et 43 séances (17 %) dans le groupe APRÈS ( p < 0,0001). Les durées médianes des séances étaient de 33 (13–48) heures dans le groupe AVANT et 55 (27–67) heures dans le groupe APRÈS ( p < 0,0001). Conclusion Notre programme d’amélioration de la stabilité de l’EERC a permis de réduire l’incidence des pertes de circuits par thrombose. Objectives During continuous renal replacement therapy (CRRT), circuit clotting increases nursing workload, cost of the therapy and blood loss. The aim of this study was to assess the impact of a program designed to improve CRRT stability on unexpected circuit clotting. Study design Retrospective and observational study. Patients and methods In January 2011, several changes have been adopted regarding CRRT management. Regional citrate anticoagulation, continuous hemodialysis using super high-flux membranes and a specific training for intensive care unit nurses were implemented. CRRT sessions before (year 2009 and 2010, “Before group”) and after (year 2011 and 2012, “After group”) were analyzed. The primary endpoint was the incidence of unexpected CRRT session end. Results During the study period, 401 sessions performed in 152 patients were analyzed. Sixty-three unexpected session's end (40%) occurred before and 43 (17%) after the implementation of the program ( P < 0.0001). Median filter life time was 33 (13–48) hours before and 55 (27–67) hours after ( P < 0.0001). Conclusion Our program designed to improve CRRT stability reduced filter losses by reducing unexpected circuit clotting. [ABSTRACT FROM AUTHOR]