Blood Purification In Sepsis Research Articles

Recent advances in membrane and sorbent design for blood purification in sepsis and septic shock

Recent advances in membrane and sorbent design for blood purification in sepsis and septic shock

Current clinical practice in using adjunctive extracorporeal blood purification in sepsis and septic shock: results from the ESICM “EXPLORATION” survey

BackgroundDespite a lack of clear evidence extracorporeal blood purification (EBP) is increasingly used as an adjunctive treatment in septic shock based on its biological plausibility. However, current state of praxis and believes in both efficacy and level of evidence are very heterogeneous.MethodsThe “EXPLORATION” (Current Clinical Practice in using adjunctive extracorporeal blood purification in septic shock), a web-based survey endorsed by the European Society of Intensive Care Medicine (ESICM), questioned both the current local clinical practices as well as future perspectives of EBP in sepsis and septic shock.ResultsOne hundred and two people participated in the survey. The majority of three quarters of participants (74.5%) use adjunctive EBP in their clinical routine with a varying frequency of description. Unselective cytokine adsorption (CA) (37.5%) and therapeutic plasma exchange (TPE) (34.1%) were by far the most commonly used modalities. While the overall theoretical rational was found to be moderate to high by the majority of the participants (74%), the effectively existing clinical evidence was acknowledged to be rather low (66%). Although CA was used most frequently in clinical practice, both the best existing clinical evidence endorsing its current use (45%) as well the highest potential to be explored in future clinical trials (51.5%) was attributed to TPE.ConclusionsAlthough the majority of participants use EBP techniques in their clinical practice and acknowledge a subjective good theoretical rationale behind it, the clinical evidence is assessed to be limited. While both CA and TPE are by far the most common used technique, both clinical evidence as well as future potential for further exploration in clinical trials was assessed to be the highest for TPE.

Renal replacement and extracorporeal therapies in critical care: current and future directions

There are a wide number of indications for extracorporeal therapies in the critical care environment. A common indication seen by the acute physician is continuous renal replacement therapy (CRRT) in a proportion of patients with acute kidney injury. It is therefore important that acute physicians have a sound understanding of the principles of CRRT in the acutely unwell patient. This review will outline the indications for its use, commonly used methods and anticoagulation considerations. It will discuss when to start and stop CRRT as well as describing potential treatment complications. This review will also discuss the role of therapeutic plasma exchange in critical care and novel extracorporeal therapies including blood purification in sepsis and carbon dioxide removal in acute respiratory distress syndrome and acute exacerbations of obstructive lung disease. Extracorporeal membrane oxygenation is outside of the scope of this article.

Blood purification in sepsis and systemic inflammation.

Sepsis and septic shock are life-threatening diseases with high mortality. Although efforts have made to improve the survivals, the outcomes are still frustrating. Blood purification was thought to be a promising adjunctive therapy to regulate the excessive cytokine storm or to reduce the endotoxin activity caused by sepsis. Critically ill COVID-19 characterized with the similar disease to sepsis may also benefit from blood purification. The recent studies mainly focused on hemadsorption materials. The results of the clinical trials showed a tendency in decrease of cytokine levels and endotoxin activity and improvement in haemodynamics. However, the results were controversial. More evidence about blood purification in sepsis and COVID-19 are needed from currently ongoing trials and future well designed trials. The blood purification therapy demonstrated the tendency in decrease of cytokines and endotoxin activity in different degree according to the current studies. However, the effect on mortality and haemodynamics is still in controversy. Further well designed, large sample sized studies should focus on the timing of initiating blood purification, the appropriate indications and the optimal type of blood purification membrane or cartridge to provide more evidence for clinical practice.

Continuous renal replacement therapy under special conditions like sepsis, burn, cardiac failure, neurotrauma, and liver failure.

Continuous renal replacement therapy (CRRT) in sepsis does have a role in removing excessive fluid, and also role in removal of mediators although not proven today, and to allow fluid space in order to feed. In these conditions, continuous renal replacement therapy can improve morbidity but never mortality so far. Regarding sepsis, timing has become a more important issue after decades and is currently more discussed than dosing. Rationale of blood purification has evolved a lot in the last years regarding sepsis with the discovery of many types of sorbent allowing ideas from science fiction to become reality in 2021. Undoubtedly, COVID-19 has reactivated the interest of blood purification in sepsis but also in COVID-19. Burn is even more dependent about removal of excessive fluid as compared to sepsis. Regarding cardiac failure, ultrafiltration can improve the quality of life and morbidity when diuretics are becoming inefficient but can never improve mortality. Regarding brain injury, CRRTs have several advantages as compared to intermittent hemodialysis. In liver failure, there have been no randomized controlled trials to examine whether single-pass albumin dialysis offers advantages over standard supportive care, and there is always the cost of albumin.

Change in blood purification for sepsis

Change in blood purification for sepsis

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications.

This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis.

ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOTÁ CONSENSUS.

Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers.

Esperienza di aferesi nelle unità intensive

Introduzione. La sepsi è una delle principali cause di morte in tutto il mondo nei pazienti ricoverati in Terapia Intensiva e, in molti casi, è associata a insufficienza renale e/o di un altro organo. Tuttavia, non esiste una terapia efficace per ridurre questo tasso di mortalità estremamente elevato. Negli ultimi anni, l'interesse intorno all'utilizzo di tecniche extracorporee di emopurificazione è aumentato. Uno dei trattamenti emergenti nei pazienti con sepsi grave e shock settico è la CPFA, una nuova terapia extracorporea di emopurificazione finalizzata a una riduzione non selettiva dei livelli circolanti e delle attività dei mediatori sia proinfiammatori che antinfiammatori. Lo scopo di questo studio è stato di osservare gli effetti della CPFA nei pazienti settici sulla mortalità e su alcuni parametri di laboratorio ed emodinamici. Pazienti e Metodi. Abbiamo trattato con CPFA 65 pazienti (50 maschi e 15 femmine). La pressione arteriosa media (MAP), il SOFA score e F APACHE II score sono stati monitorati. Sono stati dosati i livelli sierici di Interleuchina-6 e di procalcitonina. Risultati. Abbiamo osservato una mortalità di 24 pazienti (36.9%) a 28 giorni e una significativa riduzione di IL-6, di procalcitonina e dei SOFA e APACHE II score. Conclusioni. La CPFA rappresenta una nuova e promettente terapia da utilizzare nei pazienti con sepsi.

The Experience of Blood Purification in Sepsis by Coupled Plasma Filtration Adsorption in Thailand

Sepsis is an inflammation syndrome which is caused by severe infection. This severe inflammation is characterized by vasodilatation, leukocyte accumulation and increased microvascular permeability. The pathophysiology of sepsis is believed to be due to the dysregulation of the inflammatory response. The human body generates and releases a massive uncontrolled amount of proinflammatory mediators into the blood stream which causes cellular and tissue injury. This injury leads to the development of multiple organ dysfunction syndromes (MODS), and causes life-threatening conditions.

Super high-flux continuous hemodialysis: an efficient compromise for blood purification in sepsis

High cut-off membranes are proposed for blood purification therapy in septic shock. However, albumin loss related to these membranes is a major drawback limiting their clinical acceptance. Super High-Flux membranes with an optimized cut-off may combine enhanced middle molecule clearances (inflammatory mediators) with limited albumin loss. The aim of our study was to compare small, middle molecule clearances and albumin loss between continuous hemodialysis using a Super High-Flux membrane (SHF-HD) and conventional continuous hemofiltration (CVVH).

Clinical review: Blood purification for sepsis

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.

Coupled plasma filtration adsorption

Severe sepsis and septic shock are perhaps the major cause of morbidity and mortality in Intensive Care. Their pathogenesis is only partly understood. Circulating peptides and lipid-derived substances (so-called mediators), however, appear to participate in the development of organ dysfunction. It might be possible to treat plasma in such a way that the injurious effect of mediators can be attenuated. Several ex vivo studies have shown that it is technically possible to adsorb mediators by means of specially developed sorbents. The application of these sorbents to the treatment of plasma in animals with experimental sepsis has shown that several markers of inflammation can be attenuated and that animal survival can be increased. We have recently transferred such technology to the treatment of human septic shock using a technique called Coupled Plasma Filtration Adsorption (CPFA). CPFA was found to attenuate the hypotension of septic shock and to dramatically alter the immuno-paralytic toxicity of septic plasma. Monocytes of patients treated with CPFA underwent a major improvement in their ability to respond to endotoxin. CPFA represents a promising new approach to blood purification in sepsis. The findings associated with its application to humans highlight the importance of continuing to investigate blood purification as a possible approach to the treatment of septic shock, the potential usefulness of the humoral theory of sepsis, and the dominant state of immunosuppression associated with established septic shock.

Hémofiltration et choc septique : impact hémodynamique

Hémofiltration et choc septique : impact hémodynamique

Cytokine dialysis: an ex vivo study.

To test the hypothesis that dialysis using a new large pore membrane would achieve effective cytokine removal, blood from six volunteers was incubated with endotoxin (1 mg) and then circulated through a closed circuit with a polyamide membrane (nominal cut-off: 100 kDa). Hemodialysis was conducted at 1 or 9 L/hr of dialysate flow at the start of circulation and after 2 and 4 hours. The peak dialysate/plasma concentration ratios were 0.92 for interleukin (IL)-1beta, 0.67 for IL-6, 0.94 for IL-8, 0.33 for tumor necrosis factor (TNF)-a, and 0.11 for albumin. The dialysate/plasma ratios for all cytokines and albumin were decreased with increased dialysate flow from 1 to 9 L/hr (p < 0.05). Clearances for IL-1beta, IL-6, and IL-8, however, were significantly improved with increased dialysate flow (p < 0.01). There was no increase in TNF-a clearance (not significant) and a decrease in albumin clearance (p < 0.01). The peak clearance at 9 L/hr was 33 ml/min for IL-1beta, 19 for IL-6, 51 for IL-8, 11 for TNF-alpha, and 1.2 for albumin. No adsorption of cytokines was observed. We conclude that cytokine dialysis is achievable through a membrane with a high cut-off point with negligible albumin loss. These findings support the technical feasibility of this new approach to blood purification in sepsis.

Endotoxin and cytokine removal in sepsis.

Sepsis, the leading cause of mortality in intensive care units, is a complex series of interrelated effects caused by the overproduction of multiple mediators and their unrestrained biological activity. Both proinflammatory and antiinflammatory mediators participate in the high complexity of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as therapeutic options and as tools for blood purification in sepsis. Along these lines and in order to achieve higher clearances and mass removal rates, we studied the effects of plasmafiltration coupled with adsorption and provided in vitro and in vivo evidence that adsoprtion of multiple cytokines, activated complement components, and lipid mediators such as the platelet-activating factor occurs. We also showed that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics, reduced norepinephrine dose, and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma, as a modular device to conventional hemofiltration, may pave the way to innovative approaches in the extracorporeal treatment of septic patients.

Blood purification in sepsis: reasonable scientific hypothesis or pipe dream?

Blood purification in sepsis: reasonable scientific hypothesis or pipe dream?

High-volume hemofiltration.

The use of continuous hemofiltration has increased dramatically since its first description in 1977. It is now the dominant form of renal replacement therapy in Australia and is fast reaching a similar status in many European countries. Its growing use and the frequent observation of its beneficial effects in septic patients has directed the attention of researchers toward its application in the field of blood purification for sepsis. In this context, experimental studies have suggested that increasing the volume of ultrafiltrate produced may increase the beneficial effects of continuous hemofiltration. This so-called high-volume hemofiltration (HVHF) has now been demonstrated to have striking beneficial effects on hemodynamics in porcine septic shock. It has also been shown to attenuate gastrointestinal mucosal reperfusion injury in a model of gut ischemia. Furthermore, the infusion of ultrafiltrate obtained during HVHF into healthy pigs induces profound hypotension and myocardial depression, suggesting that vasodilatory and myocardial depressant substances may be removed during the procedure. Such animal experiments have led clinicians to conduct their first interventions with HVHF in humans with the multi-organ dysfunction syndrome and septic shock. The initial results are promising. They open up a new area for the investigation of HVHF as an adjuvant therapy in the management of severe sepsis, septic shock, and the multi-organ dysfunction syndrome.

High volume hemofiltration

The use of continuous hemofiltration has increased dramatically since its first description in 1977. It is now the dominant form of renal replacement therapy in Australia and is fast reaching a similar status in many European countries. Its growing use and the frequent observation of its beneficial effects in septic patients has directed the attention of researchers toward its application in the field of blood purification for sepsis. In this context, experimental studies have suggested that increasing the volume of ultrafiltrate produced may increase the beneficial effects of continuous hemofiltration. This so-called high-volume hemofiltration (HVHF) has now been demonstrated to have striking beneficial effects on hemodynamics in porcine septic shock. It has also been shown to attenuate gastrointestinal mucosal reperfusion injury in a model of gut ischemia. Furthermore, the infusion of ultrafiltrate obtained during HVHF into healthy pigs induces profound hypotension and myocardial depression, suggesting that vasodilatory and myocardial depressant substances may be removed during the procedure. Such animal experiments have led clinicians to conduct their first interventions with HVHF in humans with the multi-organ dysfunction syndrome and septic shock. The initial results are promising. They open up a new area for the investigation of HVHF as an adjuvant therapy in the management of severe sepsis, septic shock, and the multi-organ dysfunction syndrome.