Endotoxin and cytokine removal in sepsis (original) (raw)
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Kidney International, 2012
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.
Critical Care, 2018
Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cutoff (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.
Roles of extracorporeal blood purification in sepsis
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2007
Severe sepsis represents the leading cause of mortality and morbidity in critically ill patients. Although the authors' understanding of the complex pathophysiological alterations that occur in severe sepsis and septic shock has increased greatly, mortality associated with the disorder remains unacceptably high. Recent treatment guidelines have reinforced the importance of early goal directed therapy. Recently, moderate doses of corticosteroid replacement and activated protein C (drotrecogin alfa[activated]) are the therapies demonstrating efficacy. Extra-corporeal blood purification techniques offer a variety of techniques that can efficiently eliminate septic mediators. The rationale for its use in sepsis is sound Animal and human studies show promise with improvements in hemodynamics and mortality, but are limited by number and design. These techniques require large-scale well-conducted studies to demonstrate the validity in sepsis.
Continuous Hemodiafiltration with a Cytokine-Adsorbing Hemofilter for Sepsis
Blood Purification, 2012
Since the introduction of the new pathophysiological concept of pathogen-associated molecular patterns (PAMPS) and alarmins, endotoxin has been recognized as only one of the PAMPS. It is widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. Many kinds of blood purification modalities have been proposed as a therapeutic tool against sepsis, including high-volume continuous hemofiltration whose efficacy has recently been questioned. We report that continuous hemodiafiltration (CHDF) with a cytokine-adsorbing hemofilter (CAH), such as polymethyl methacrylate hemofilter and AN69ST hemofilter (CAH-CHDF), can remove many kinds of cytokines and has been very effective in the treatment of severe sepsis and septic shock. Based on the understanding of the recent pathophysiology, we suggest that CAH-CHDF is an alternate therapy to direct hemoperfusion with endotoxin-adsorbing column in the treatment of sepsis.
Kidney International, 2000
Adsorption in sepsis. The pathophysiology of sepsis offers a ride (LPS), trigger a global response that involves both highly complicated scenario. In sepsis, endotoxin or other cellular and humoral pathways with the generation of program-positive-derived products induce a complex and dynamic inflammatory and anti-inflammatory mediators [5, 7, 8]. cellular response, giving rise to several mediators known to be These include a major group of middle molecular size relevant in the pathogenesis of septic shock such as specific (5 to 30 kD) peptides, collectively called cytokines, phosmediators, substances responsible for up-or down-regulation of cytokine receptors and cytokine antagonists, inactivators of pholipase A 2-dependent products such as platelet-actitranslational or transductional pathways, and precursor molevating factor (PAF), leukotrienes, and thromboxanes, cules. In this review, we delve into some new concepts stemand complement-derived activated products such as C3a, ming up from the use of sorbents in continuous plasma filtra-C5a, and their desarginated products. Other agents tion. Nonspecific simultaneous removal of several mediators of the inflammatory cascade have led to improved outcomes play a role in the pathophysiology of sepsis such as surin animal models of septic shock and to improved hemodynamface-expressed and soluble adhesion molecules, kinins, ics in a pilot clinical study. It seems of great importance to thrombin, myocardial depressant substance(s), -endorexplore all possible treatment techniques that may have a direct phin, and heat shock proteins. In normal conditions, the impact on circulating mediators of sepsis and that also may biological activity of these mediators is under the control interfere with the imbalance between proinflammatory and anti-inflammatory substances in the critically ill patient with
Can the Reduction of Cytokines Stop the Progression of Sepsis?
Cureus
In this study, we aimed to analyze the laboratory and clinical results of cytokine hemadsorption as an immunomodulation therapy in ICU patients diagnosed with sepsis or septic shock. Methods The levels of procalcitonin (PCT) and C-reactive protein (CRP), determined to be indicators of infection/sepsis, and the levels of interleukins (IL-6, IL-8, and IL-10) and tumor necrosis factor α (TNFα), deemed as indicators of the cytokine storm, were compared among 32 patients before and after the hemadsorption procedure. Results The hemadsorption significantly reduced the levels of IL-6, IL-8, IL-10, TNFα, PCT, CRP, Acute Physiology and Chronic Health Evaluation (APACHE) scores, mortality rate, and Sequential Organ Failure Assessment (SOFA) scores (p<0.05). APACHE scores and the mean predicted mortality rate (PMR) of the non-survivors measured before the procedure was significantly higher than those of survivors (p=0.002 for both). IL-10, APACHE scores, and the mortality rates determined before the hemadsorption procedure were deemed significant parameters to predict the mortality among all ICU patients (p<0.05). IL-10 levels ≤125.3 ng/L, APACHE score >30, and PMR >70.33 were significantly associated with the mortality rates of all patients, indicating that these three parameters determined before the hemadsorption may be good predictors of mortality among ICU patients with sepsis. Conclusion The progression of sepsis in ICU patients may be prevented with cytokine hemadsorption applied as an immunomodulator therapy.
Accepted for publication on September 14, 2007. SEPSIS: FROM BENCH TO BEDSIDE
2014
Sepsis is a syndrome related to severe infections. It is defined as the systemic host response to microorganisms in previously sterile tissues and is characterized by end-organ dysfunction away from the primary site of infection. The normal host response to infection is complex and aims to identify and control pathogen invasion, as well as to start immediate tissue repair. Both the cellular and humoral immune systems are activated, giving rise to both anti-inflammatory and proinflammatory responses. The chain of events that leads to sepsis is derived from the exacerbation of these mechanisms, promoting massive liberation of mediators and the progression of multiple organ dysfunction. Despite increasing knowledge about the pathophysiological pathways and processes involved in sepsis, morbidity and mortality remain unacceptably high. A large number of immunomodulatory agents have been studied in experimental and clinical settings in an attempt to find an efficacious anti-inflammatory ...