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Pieter Evenepoel - One of the best experts on this subject based on the ideXlab platform.
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a prospective randomized open label crossover trial of regional citrate anticoagulation vs anticoagulation free Liver Dialysis by the molecular adsorbents recirculating system
Critical Care, 2012Co-Authors: Bjorn Meijers, Wim Laleman, Pieter Vermeersch, Frederik Nevens, Alexander Wilmer, Pieter EvenepoelAbstract:Introduction: The Molecular Adsorbent Recycling System (MARS) is used to treat patients with Liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods: We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with Liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher’s exact test was used for contingency table analysis. Results: Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher’s exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions: Regional citrate anticoagulation in patients with Liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with Liver failure.
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stability of therapeutic albumin solutions used for molecular adsorbent recirculating system based Liver Dialysis
Artificial Organs, 2012Co-Authors: Tom De Bruyn, Bjorn Meijers, Pieter Evenepoel, Ruth Laub, Ludo Willems, Patrick Augustijns, Pieter AnnaertAbstract:Mounting evidence suggests beneficial effects of albumin Dialysis-based Liver support in patients suffering from acute-on-chronic Liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological Liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier-specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure.
John R Lake - One of the best experts on this subject based on the ideXlab platform.
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treatment of hepatic failure 1996 current concepts and progress toward Liver Dialysis
American Journal of Kidney Diseases, 1996Co-Authors: Norman Sussman, John R LakeAbstract:Liver failure, especially in its acute form, is a medical emergency that quickly leads to failure of multiple other organs. Many of these end-organ failures can be supported temporarily by drugs or medical devices, but the support is invariably short-lived if Liver function is not restored. In most instances, Liver function can only be restored by transplantation, although patients with acute disease have the potential to recover by regeneration ("spontaneous recovery"). Unfortunately, spontaneous recovery from acute Liver failure is uncommon, so the two most important aspects of patient management are highly skilled intensive care and early recognition of patients in need of Liver transplantation. Even under these circumstances, the mortality of Liver failure remains high because we have no easy way of replacing Liver function on demand and donor organs are becoming increasingly difficult to obtain in time. The development of techniques for Liver assist offer the possibility that patients with Liver failure will become a simple management problem, analogous to the options available in the treatment of acute and chronic renal failure.
Bjorn Meijers - One of the best experts on this subject based on the ideXlab platform.
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a prospective randomized open label crossover trial of regional citrate anticoagulation vs anticoagulation free Liver Dialysis by the molecular adsorbents recirculating system
Critical Care, 2012Co-Authors: Bjorn Meijers, Wim Laleman, Pieter Vermeersch, Frederik Nevens, Alexander Wilmer, Pieter EvenepoelAbstract:Introduction: The Molecular Adsorbent Recycling System (MARS) is used to treat patients with Liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods: We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with Liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher’s exact test was used for contingency table analysis. Results: Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher’s exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions: Regional citrate anticoagulation in patients with Liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with Liver failure.
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stability of therapeutic albumin solutions used for molecular adsorbent recirculating system based Liver Dialysis
Artificial Organs, 2012Co-Authors: Tom De Bruyn, Bjorn Meijers, Pieter Evenepoel, Ruth Laub, Ludo Willems, Patrick Augustijns, Pieter AnnaertAbstract:Mounting evidence suggests beneficial effects of albumin Dialysis-based Liver support in patients suffering from acute-on-chronic Liver failure. Molecular adsorbent recirculating system (MARS) is a nonbiological Liver support device, based on the exchange of albumin-bound toxins between the patient's blood and a 20% human serum albumin solution in a secondary circuit. Bound toxins are continuously removed from the circulating albumin by exposure to activated charcoal and an ion-exchange resin. The aim of the present in vitro study was to determine the impact of exposure to charcoal and resin on the ligand binding properties of albumins, containing various levels of stabilizers and obtained from different suppliers (Baxter, CAF-DCF [Red Cross], and Sigma-Aldrich). Albumin binding properties were assessed by measuring equilibrium binding properties of warfarin, diazepam, and salicylate before and after incubation (for up to 7 h) with adsorbing materials; albumin-associated esterase-like activities were also determined. Notable changes in albumin binding upon incubation with adsorbing materials were only observed when using warfarin as a ligand. Affinity of warfarin for the Baxter and Sigma albumins showed a pronounced decrease (higher K(d) ) after the 1-7-h exposure to charcoal or resin. In the absence of adsorbing materials, similar effects were found, indicating that incubation time per se affects albumin binding properties. Following exposure to resin, Baxter albumin binding capacity (B(max)) increased about twofold. For albumin obtained from CAF-DCF, binding affinity and capacity for warfarin were constant under all conditions tested. Esterase-like activities associated with these albumins were either maintained or enhanced (up to 2.5-fold in case of Sigma albumin) following 7-h incubations with adsorbing materials. Our data suggest limited direct influence of the presence of stabilizers in therapeutic albumin solutions on baseline binding properties of human albumin. However, in vitro incubations of these albumins for several hours resulted in supplier-specific changes in warfarin binding, suggesting an influence of stabilizers on the stability of binding properties. Further preclinical and clinical studies are required to elucidate the clinical relevance of these in vitro results, that is, to what extent these changes in albumin binding properties result in altered performance of albumins in the secondary circuit during the MARS procedure.
Peter Krisper - One of the best experts on this subject based on the ideXlab platform.
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technology insight artificial extracorporeal Liver support how does prometheus compare with mars
Nature Reviews Nephrology, 2007Co-Authors: Peter Krisper, R StauberAbstract:Here, Krisper and Stauber analyze the relative efficiency, clinical outcomes, safety and potential indications of two different 'Liver Dialysis' systems. Despite their 'experimental' status, the Molecular Adsorbents Recirculating System (MARS®) and Prometheus®, developed by Gambro and Fresenius Medical Care, respectively, are increasingly used to treat patients with severe hepatic failure. Preliminary data are promising, and large-scale randomized trials with the aim of proving a survival benefit are underway. Artificial extracorporeal Liver support or 'Liver Dialysis' has been used in patients with severe Liver failure with increasing frequency since the Molecular Adsorbents Recirculating System (MARS®), a variant of albumin Dialysis, was introduced in 1999. Nevertheless, Liver Dialysis must still be thought of as experimental because its contribution to improved patient survival has not been proven in large randomized trials. Prometheus® is a novel device for fractionated plasma separation via an albumin-permeable filter that was developed to improve removal of albumin-bound toxins. Initial studies have proven clinical use of Prometheus® to be feasible and safe. Head-to-head comparisons of Prometheus® and MARS® have shown treatment with the former to be more efficient with respect to removal of most albumin-bound and water-solved markers. As controlled studies with clinical end points are lacking, it is not known whether the observed greater detoxification capacity of Prometheus® will translate into clinical benefit; two small studies indicate that there might be a beneficial effect in hepatic encephalopathy and pruritus. In a recent randomized comparison of MARS® and Prometheus®, however, hemodynamic improvement was observed in response to MARS®, but not Prometheus®, treatment. A large randomized controlled trial investigating the effect of Prometheus® on survival—the HELIOS study—has been initiated. First results are expected in 2008 and will be crucial to establishing a role for Prometheus® in the field of extracorporeal Liver support.
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in vivo quantification of Liver Dialysis comparison of albumin Dialysis and fractionated plasma separation
Journal of Hepatology, 2005Co-Authors: Peter Krisper, Bernd Haditsch, Rudolf E Stauber, Aleksandra Jung, Vanessa Stadlbauer, Michael Trauner, Herwig Holzer, Daniel SchneditzAbstract:Background/Aims Artificial Liver support represents a potentially useful option for the treatment of severe Liver failure. A sufficient ‘dose' might be crucial for such treatments to provide a survival benefit. The aim of this study was to compare in vivo efficiency and resulting deLivered treatment dose of two commercially available devices that use different therapeutic principles: albumin Dialysis (AD, MARS ® ) and fractionated plasma separation (FPS, Prometheus ® ). Methods Eight patients with acute-on-chronic Liver failure were treated alternately with AD and FPS. Thirty-two treatments at identical blood and dialysate flow rates were evaluated. Clearance and reduction ratio (a measure of deLivered treatment dose) were compared for bilirubin subfractions, ammonia and urea. Results FPS achieved significantly higher clearance for all measured protein-bound and water-soluble markers. This resulted in significantly higher reduction ratios for FPS compared to AD. Unconjugated bilirubin, a marker for strongly albumin-bound toxins, was influenced only by FPS. Conclusions FPS provided a higher deLivered treatment dose than a matching treatment with AD. Reduction ratios of bilirubin and urea should be reported in clinical studies on Liver Dialysis, since deLivered dose is likely to be linked to the clinical effectiveness of extracorporeal Liver support therapies.
Norman Sussman - One of the best experts on this subject based on the ideXlab platform.
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treatment of hepatic failure 1996 current concepts and progress toward Liver Dialysis
American Journal of Kidney Diseases, 1996Co-Authors: Norman Sussman, John R LakeAbstract:Liver failure, especially in its acute form, is a medical emergency that quickly leads to failure of multiple other organs. Many of these end-organ failures can be supported temporarily by drugs or medical devices, but the support is invariably short-lived if Liver function is not restored. In most instances, Liver function can only be restored by transplantation, although patients with acute disease have the potential to recover by regeneration ("spontaneous recovery"). Unfortunately, spontaneous recovery from acute Liver failure is uncommon, so the two most important aspects of patient management are highly skilled intensive care and early recognition of patients in need of Liver transplantation. Even under these circumstances, the mortality of Liver failure remains high because we have no easy way of replacing Liver function on demand and donor organs are becoming increasingly difficult to obtain in time. The development of techniques for Liver assist offer the possibility that patients with Liver failure will become a simple management problem, analogous to the options available in the treatment of acute and chronic renal failure.