Newly Designed CRRT Membranes for Sepsis and SIRS—A Pragmatic Approach for Bedside Intensivists Summarizing the More Recent Advances

Honoré, Patrick M.; Jacobs, Rita; Joannès-Boyau, Olivier; Regt, Jouke De; Waele, Elisabeth De; Gorp, Viola Van; Boer, Willem; Verfaillie, Lies; Spapen, Herbert

doi:10.1097/mat.0b013e3182816a75

Cited by 135 publications

(117 citation statements)

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“…Early saturation is unlikely and frequent membrane changes (e.g. every 12-24 h) are not necessary [17,19]. This is corroborated by our experience in a small cohort of patients who supported colistin doses as high as 4.5 million IU t.i.d.…”

Section: Crrt-related Strategies To Avoid Colistin Toxicitysupporting

confidence: 69%

“…In contrast, the novel AN69 ST (acrylonitrile 69 surface treated) membrane allows much higher clearance through adsorption. Elimination occurs in part at the (rapidly saturated) membrane surface but predominantly in its (less easily saturated) bulk [19]. Early saturation is unlikely and frequent membrane changes (e.g.…”

Section: Crrt-related Strategies To Avoid Colistin Toxicitymentioning

confidence: 99%

“…This explains the absence of colistin toxicity during CRRT even when the aforementioned high doses are administered for a long time period. Still, caution is needed since not all currently used membranes have similar adsorptive capacity [19]. …”

Section: Colistin Handling During Crrt and Its Relation To Efficacy Amentioning

confidence: 99%

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Continuous Renal Replacement Therapy-Related Strategies to Avoid Colistin Toxicity: A Clinically Orientated Review

et al. 2014

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Polymyxins are ‘old' antimicrobials which were abandoned for almost 30 years because of significant renal and neurological toxicity. However, the alarming rise in multiresistant Gram-negative bacterial infections worldwide has revived interest in these ‘forgotten' agents. Colistin (polymyxin E) is one of the main antibiotics of this class. It is most often administered as the prodrug colistimethate sodium. Doses for treatment of systemic infections in adults range between 3 and 9 million IU per day. Colistin is increasingly used to treat pneumonia and bacteremia in critically ill patients. During their intensive care unit stay, many of these patients will need continuous renal replacement therapy (CRRT) because of acute kidney injury or an unstable hemodynamic condition. Based on recent pharmacological data and our own experience, we postulate that patients undergoing CRRT may receive substantially higher doses of colistin (i.e. a high loading dose, followed by a maintenance dose of up to 4.5 million IU t.i.d.). Treatment can be continued for a prolonged time period without increasing toxicity. CRRT counteracts colistin accumulation because the drug is continuously filtered and also significantly adsorbed in the bulk of the dialysis membrane. Implementing such a ‘CRRT rescue' therapy does require the strict use of highly adsorptive dialysis membranes in association with citrate anticoagulation to increase membrane performance.

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Section: Crrt-related Strategies To Avoid Colistin Toxicitysupporting

confidence: 69%

Section: Crrt-related Strategies To Avoid Colistin Toxicitymentioning

confidence: 99%

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Continuous Renal Replacement Therapy-Related Strategies to Avoid Colistin Toxicity: A Clinically Orientated Review

et al. 2014

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“…In Switzerland, an RCT that compares the efficacy of oXiris®-CVVH and PMX-DHP in patients with septic shock is currently in progress (ENDoX study). Furthermore, Honore et al state in their review article that they are planning an RCT to compare four different membrane hemofilters (AN69, AN69ST, oXiris®, and PAES) in septic shock with AKI [48].…”

Section: Modified An69st (Oxiris®)mentioning

confidence: 99%

Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury

Hattori

Oda

2016

Ren Replace Ther

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While evidence supporting the hypothesis that blood purification improve outcome in septic acute kidney injury (AKI) has not been established, many physicians hope to improve outcome in septic AKI by blood purification. Elucidation of the pathophysiology of sepsis has revealed close involvement of humoral mediators, including cytokines, pathogen-associated molecular patterns, and alarmins, in the development of severe sepsis. Removal of substances by blood purification involves three major principles, namely filtration, dialysis (diffusion), and adsorption. Multiple large randomized controlled trials (RCTs) of high-volume hemofiltration (HVHF) for patients with AKI were conducted, but failed to prove the clinical efficacy of HVHF. Blood purification for the removal of mediators through dialysis and filtration using a high cutoff (HCO) membrane hemofilter has not also been established. Furthermore, a HCO membrane hemofilter shares a common problem with HVHF, which is excessive removal of useful substances, such as antimicrobial agents and/or nutrients. Accordingly, continuous hemodiafiltration using cytokine-adsorbing hemofilters (CAH-CHDF) such as polymethylmethacrylate (PMMA) and AN69ST membrane hemofilters has been attracting attention recently. In this review, we report recent findings regarding these old hemofilters with new applications. Although the number of in vitro and in vivo studies conducted to date has been limited, the studies suggest a possibility that these modalities are useful particularly for the treatment of septic shock and septic AKI. CAH-CHDF is expected to be recognized globally as a treatment of septic shock and septic AKI in the near future.

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“…Nosaka et al recently showed that administration of a monoclonal antibody against HMGB-1 suppressed the immuno-inflammatory response and significantly improved severe lung injury and survival in patients affected with H1N1 influenza A virus [15]. HMGB-1 is also effectively cleared by highly adsorptive dialysis membranes such as the acrylonitrile 69 surface-treated filter [16] which is increasingly used for continuous renal replacement therapy (CRRT) in hemodynamically unstable septic patients [17]. Though obviously an attractive and more easily available alternative for counteracting the noxious effects of HMGB-1, clinical efficacy and benefit of such CRRT approach has not yet been established.…”

mentioning

confidence: 99%

Nobiletin: A Citrus Isolate to Make Sepsis Less Sour

et al. 2016

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Septic shock remains a major concern in critically ill patients. Morbidity, as reflected by cardiovascular instability and sequential organ failure, is high and mortality ranges from 20 to 50 % [1]. Treatment options are scarce and mainly causeoriented and symptomatic. Substantial efforts to control the coordinate but sometimes profuse and potentially lethal sepsis-induced immuno-inflammatory response remained unsuccessful. Indeed, large studies investigating numerous "magic bullets" interfering with sepsis-related immuneinflammatory or coagulation processes failed to show efficacy on relevant outcome parameters [2][3][4]. Also, the theoretical benefit of blood purification by restoring immune homeostasis through indiscriminate removal of inflammatory mediators could not be confirmed [5].In this context, the paper of Li et al. is highly welcomed. The authors convincingly demonstrate a protective effect of nobiletin, a citrus flavone present in the peels of tangerine, mandarin and oranges, in murine endotoxic shock [6]. Interestingly, apart from inhibiting the "usual pro-inflammatory suspects" tumor necrosis factor-α and interleukin (IL)-6, the study focuses on two key protagonists within the sepsis cascade: high mobility group box-1 (HMGB-1) protein and nuclear factor kappa B (NF-κB) [6].HMGB-1 is a late mediator of endotoxin lethality [7] and perfectly fits all criteria for an "alarmin" [8]. Alarmins form the endogenous branch of the larger family of damage-associated molecular patterns (DAMPs) that are released by threatened, injured, or necrotic cells [9]. In the nucleus, HMGB-1 stabilizes nucleosome formation and facilitates transcription factor binding. Outside the cell, it functions as a cytokine with weak direct pro-inflammatory activity [10] but considerable ability for indirect triggering of inflammation [11]. HMGB-1, indeed, acts as a potent chemoattractant for neutrophils, monocytes, macrophages, and dendritic cells and engages, among others, Toll-like, IL-1, and receptors for advanced glycation end-products (RAGE) that sustain or enhance the inflammatory process. Moreover, HMGB-1 and endotoxin synergistically reinforce each other at both receptor level and in activating transcriptional responses [11]. Severe sepsis [12] and acute inflammatory lung injury [13] are associated with lifethreatening out-of-control HMGB-1 responses. Thus, it makes perfect sense that measures for keeping the HMGB-1 release in check may dramatically influence the course of sepsis. Inhibiting HMGB-1 in murine sepsis protected against development of organ injury and reversed lethality [14]. Nosaka et al. recently showed that administration of a monoclonal antibody against HMGB-1 suppressed the immuno-inflammatory response and significantly improved severe lung injury and survival in patients affected with H1N1 influenza A virus [15]. HMGB-1 is also effectively cleared by highly adsorptive dialysis membranes such as the acrylonitrile 69 surface-treated filter [16] which is increasingly used for continuous renal replacement ther...

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Newly Designed CRRT Membranes for Sepsis and SIRS—A Pragmatic Approach for Bedside Intensivists Summarizing the More Recent Advances

Cited by 135 publications

References 50 publications

Continuous Renal Replacement Therapy-Related Strategies to Avoid Colistin Toxicity: A Clinically Orientated Review

Continuous Renal Replacement Therapy-Related Strategies to Avoid Colistin Toxicity: A Clinically Orientated Review

Cytokine-adsorbing hemofilter: old but new modality for septic acute kidney injury

Nobiletin: A Citrus Isolate to Make Sepsis Less Sour

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