Blood Purification最新文献

Background: Patients with metastatic cancer are at risk of drug-related toxicity or disease-related complications leading to the development of organ failure such as rhabdomyolysis-associated acute kidney injury (AKI), liver failure, and multi-organ failure, often precipitated by endotoxinemia and sepsis. In cases of systemic hyperinflammatory response, mediated by cytokines, to specific treatment with CAR-T-cell therapy or in sepsis with or without the development of AKI, we do not have an effective and specific target molecule-oriented therapy.

Summary: Over the past few decades, numerous experimental and clinical studies have investigated the efficacy of extracorporeal blood purification technologies in the treatment of specific indications like sepsis and septic shock. In this review article, our goal was to show the possibility of using different hemoadsorbers in specific indications in patients with cancer-related complications, their reported effectiveness in certain indications and the possibility of applying it to cancer patients not only as a last-stand therapy but as well as preventing the development of specific organ or multi-organ failure.

Key messages: Currently, multiple forms of extracorporeal blood purification are available that may have benefit in patients with cancer-related complications. Despite a strong rationale for extracorporeal blood purification, many physicians are still reluctant introducing hemoadsorption as a recommended routine due to still insufficient evidence, mostly as a result of inadequate numbers of published randomized controlled trials. Nevertheless, the application of hemoadsorption should be the same for cancer-related complications as well as it is for other patients because, in most cases, we aim to remove the same target molecules.

Background: Burns are a common injury affecting thousands of people worldwide each year. Clinical severity varies according to the total body surface area burned, which is in turn associated with morbidity and mortality. The management of a severe burn patient requires admission to a referral center. Patients with severe burns exhibit a complex and dysregulated immuno-inflammatory response. This leads to the loss of immune homeostasis, which is a source of infectious complications and organ dysfunctions. This loss of control of immune mechanisms plays a key role in the morbidity and mortality of severe burn patients.

Summary: Currently, several strategies, such as hemoadsorption, have been developed to modulate this host response. Modern hemoadsorption is based on new highly biocompatible sorbent cartridges of neutral macroporous resin beads. We propose herein a review of the immune pathways in burn injury and the rationale and potential applications of extracorporeal blood purification techniques, such as hemoadsorption, in the management of burn patients.

Key messages: Severe burns trigger an uncontrolled immuno-inflammatory response, leading to high morbidity and mortality. Immune homeostasis loss is central to complications such as infections and organ failure. Hemoadsorption may represent a potential therapeutic option to help modulate the immune response in burn patients.

Background: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, and where underlying circulatory, cellular, and metabolic abnormalities contribute to a greater risk of mortality than that posed by sepsis alone, this may be considered septic shock where circulatory support is needed in the face of a raised lactate level. The main pillars of therapy remain source control and appropriate timely antibiotics, resuscitation where needed, and adequate source control. However, in the setting of organ failure further support may be needed.

Summary: Here, we discuss the potential benefits from removal of pathogens using available extracorporeal techniques. Although randomized controlled trials supporting such an approach remain elusive, this is due to change in the next few years with current studies being performed. The use of extracorporeal blood purification therapies is a promising therapeutic strategy for critically ill ICU patients with high pathogen load refractory to conservative treatment or with elevated endotoxin levels.

Key messages: By targeting specific inflammatory mediators and pathogens, extracorporeal blood purification can help mitigate the severe inflammatory response associated with sepsis which should translate into improved patient survival. This approach may be particularly beneficial in cases where traditional treatments fail highlighting the need for further data to optimize the use of blood purification therapies in sepsis management.

Background: The recognition of syndromes has been a pillar of medical education and knowledge. However, treatment of syndromes is challenging because there is a disconnect between the underlying mechanisms that lead to organ injury and the clinical expression of this injury. This is an important barrier to identifying effective treatments in sepsis which may be resolved by the identification of sepsis endotypes.

Summary: In this review, we discuss the rationale for considering endotoxic septic shock as a true endotype; the mechanisms by which endotoxin induce cell and organ injury and dysfunction, the strategies to recognize when it occurs and the potential treatments, focusing on endotoxin removal through extracorporeal blood purification.

Key messages: There is sufficient preclinical and clinical evidence to support the notion that endotoxin is a relevant mechanism of injury in human sepsis that drives poor patient outcomes that can be identified using clinical criteria and biomarkers and that may respond to specific targeted therapies, strongly suggesting that endotoxemic septic shock is a bona fide endotype.

Background: Haemoadsorption (HA) is increasingly recognized as a valuable extracorporeal blood purification technique in paediatric intensive care. Although initially developed for adult patients, HA's application in paediatric critical care, particularly for conditions such as septic shock, liver failure, and rhabdomyolysis, has gained significant attention due to promising clinical outcomes.

Summary: HA has demonstrated efficacy in managing paediatric septic shock by reducing vasopressor requirements and lowering inflammatory markers. In liver failure, HA complements continuous renal replacement therapy (CRRT) by removing albumin-bound toxins and cytokines, mitigating systemic inflammation. Emerging evidence also supports HA as a rescue therapy in rare paediatric conditions like rhabdomyolysis and acute intoxications, preventing organ damage and reducing morbidity. Despite its benefits, HA in paediatrics presents technical challenges, including concerns over extracorporeal circuit volumes, vascular access, and anticoagulation. Paediatric-specific devices, such as the HA60, BS80, and PMX-05R, are addressing these limitations by offering lower priming volumes suitable for small children. Recent studies have highlighted improvements in haemodynamic stability, cytokine reduction, and organ function, reinforcing HA's potential as a critical adjuvant therapy. This review underscores the evolving landscape of HA in paediatric critical care, advocating for further research to optimize its application across diverse clinical scenarios.

Key messages: (1) HA shows significant promise in paediatric septic shock, liver failure, and rhabdomyolysis. (2) Technical advancements are expanding HAs applicability to neonates and small infants. (3) More multicentre studies are needed to establish HA's role in reducing mortality and improving quality of life post-PICU.

Introduction Sepsis and sepsis-associated acute kidney injury (AKI) are associated with increased patient morbidity and mortality. The immediate host response aimed at combating infection can become dysregulated, leading to uncontrolled inflammation and multi-organ failure, including AKI. Therapies targeting one protein component of the sepsis pathway have largely failed to improve patient outcomes, and currently only organ support therapies are used clinically to provide time for innate organ recovery to occur. The Selective Cytopheretic Device (SCD) is a continuous cell processing immunomodulatory device that attracts activated neutrophils and monocytes its biomimetic membrane surface. The activated leukocytes are transformed to a less pro-inflammatory phenotype and released back into the circulation when exposed to low ionized calcium concentration established in the SCD by standard regional citrate anticoagulation protocols used in continuous renal replacement therapy. Review In this review, we detail the history of the SCD and our experience with it, from discovery to pre-clinical testing to translational research application at the bedside. We discuss the SCD mechanism of action, its immunomodulatory effect, and the human studies involving critically ill adult pediatric patients with AKI who require continuous renal replacement therapy as part of the standard of care. We conclude discussing ongoing and future application of the SCD in both acute and chronic inflammatory states that would benefit from immunomodulation.

Background: There is growing interest in hemoadsorption (HA) therapies in critically ill patients although their precise indications remain to be established. Several devices are available on the market with heterogeneous properties and capabilities.

Summary: Due to the nonspecific removal associated with most HA techniques, concerns have been raised on their unintended removal of drugs such as anti-infectives in sepsis. On the other hand, drug removal might be beneficial in certain situations for instance antithrombotic medications in patients requiring emergency surgery or in case of accidental or self-induced intoxication. In this review, we summarize available in vitro, in vivo, and clinical studies reporting on the influence of various HA techniques on drugs pharmacokinetics.

Key message: We conclude that further studies should aim at providing drug dosing recommendations during HA and confirm its safety, efficacy, and practicalities when used for intoxications.