1 The sooner the better A guide to MARS the liver support therapy
2 Liver failure and MARS therapy Developing acute liver failure or deteriorating from a chronic liver disease, thousands of people are enlisted on liver transplant waiting lists every year. With a shortage of organs, time becomes extremely important and management of these patients represents a significant challenge for physicians around the world. Gambro, the leading supplier of artificial support systems, brings you the Molecular Adsorbent Recirculating System (MARS) for the treatment of patients with liver failure. Liver patients benefit from getting support as soon as possible With early interventions, the MARS system helps prevent the evolution of irreversible multiorgan failure and facilitates an improved environment for hepatic regeneration and clinical recovery. The MARS system removes protein-bound and water-soluble toxins with albumin dialysis. This reduces plasma toxicity, improves patient clinical conditions (hemodynamics, hepatic encephalopathy, urine output), enhances the regeneration of liver cells and may help to recover native liver functions. Clinically applied since 1993, the MARS system is the most extensively used non-biological liver support therapy in the world, with an evergrowing base of clinical experience and evidence. By 2009, more than 9,000 patients from 150 centers in 30 different countries had already been treated with a safe profile, and in more than 36,000 performed treatments. Indications treated include: Acute-on-chronic liver failure Acute liver failure, including from drug overdose and poisoning Graft dysfunction after LTx Liver failure after liver surgery Secondary liver failure Intractable pruritus in cholestasis
3 The MARS system stabilizes patients and has a positive impact on: Survival 6,7,11 Hemodynamics 2,5,7,17,18 Brain function 1,6,8,9 Kidney function 7 Liver function 15,20 Liver recovery in ALF 12,13,15 Quality of life 14,21,22,23 Overall therapy costs 24,25
4 How the MARS system works The MARS system combines the efﬁcacy of sorbents to remove albuminbound toxins with the high selectivity of highly biocompatible dialysis membranes. In this way, common dialysis or CRRT machines can be expanded into a modern system for liver support therapy. The blood of the extracorporeal circuit runs through the ﬁbers of the MARS FLUX dialyzer. Water-soluble and protein-bound toxins in the blood can pass through the membrane due to the albumin dialysate on the other side. The albumin dialysate solution is free from stabilizers when dialysing the patient. The now toxin-enriched albumin solution is then passed through another dialyzer to remove water-soluble toxins. Albumin-bound toxins are removed in the two adsorber cartridges, one ﬁlled with activated charcoal, the other with an anion exchanger. The regenerated albumin solution is then ready for new uptake of toxins from the blood. Removable protein-bound and water-soluble substances 26 Blood circuit MARS AC 250 Albumin circuit DIA FLUX IE 250 Dialysis membrane MARS Activated charcoal ﬁlter Ion exchanger FLUX MARS MARS membrane Ammonia Bilirubin Bile acids Aromatic amino acids Medium and short chain fatty acids Tryptophan Copper Creatinine Urea Diazepam Dialysis circuit
5 Free low molecular weight substance ALBUMIN- DIALYSATE Dialysate albumin Albumin-related binding sites Plasmaalbumin Toxic albuminassociated compounds, e.g. bilirubin BLOOD Protein-layer MEMBRANE Section of the semi-permeable membrane. Water-soluble and albumin-bound toxins can pass through.
6 Putting you in control of your patient s therapy The MARS system is compatible with several hemodialysis machines and CRRT devices, and requires minimal staff involvement before and during treatment. Deliver the prescribed treatment with high safety standards Simultaneous selective removal of albumin-bound and water-soluble substances High effectiveness and selectivity Management of fluid, electrolyte and acid/base balance Control of glucose and lactate level High safety standards: safety barrier between patient s blood and adsorber columns, cell-free operation, high biocompatible membrane Extracorporeal blood volume limited to one filter Compatible with a wide range range of renal replacement equipment Features of dialysis and CRRT machines usable No major side-effects Cost-effective regeneration of the albumin dialysate Features Combined detoxification: interaction ion between the MARS monitor and standard CRRT or hemodialysis device. (See also List of allowed device combinations available at your local sales agent.)
7 Literature on MARS therapy. Randomized controlled trials 1. Hassanein, TI. et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology. 2007; 46(6): Laleman, W. et al. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care. 2006; 10(4):R Jalan, R. et al. Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl. 2004; 10(9): El Banayosy, A. et al. First use of the Molecular Adsorbent Recirculating System technique on patients with hypoxic liver failure after cardiogenic shock. Asaio J. 2004; 50(4): Schmidt, LE. et al. Systemic hemodynamic effects of treatment with the molecular adsorbents recirculating system in patients with hyperacute liver failure: A prospective controlled trial. Liver Transpl. 2003; 9(3): Heemann, U. et al. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.hepatology. 2002; 36: Mitzner, SR. et al. Improvement of Hepatorenal Syndrome With Extracorporeal Albumin Dialysis MARS: Results of a Prospective, Randomized Controlled Clinical Trial Liver Transpl. 2000; 6: Other clinical trials 8. Sen, S. et al. Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study. Crit Care Med. 2006; 34(1): Blei, A. et al. Albumin dialysis for the treatment of hepatic encephalopathy. Journal of Gastroenterology and Hepatology. 2004; 19(0):S224-S Faybik, P. et al. Molecular Adsorbent Recirculating System and hemostasis in patients at High risk of bleeding: an observational study. Crit Care. 2006; 10(1):R Montejo González, JC. et al. Artificial liver support system in acute liver failure patients waiting liver transplantation. Hepatogastroenterology. 2009; 56(90): Camus C. et al. Liver transplantation avoided in patients with fulminant hepatic failure who received albumin dialysis with the molecular adsorbent recirculating system while on the waiting list: impact of the duration of therapy. Ther Apher Dial. 2009;13(6): Kantola, T. et al. The effect of molecular adsorbent recirculating system treatment on survival, native liver recovery, and need for liver transplantation in acute liver failure patients. Transpl Int. 2008; 21(9): Javouhey, E. et al. Long-lasting extracorporeal albumin dialysis in a child with end-stage renal disease and severe cholestasis. Pediatr Transplant. 2008; 13(2): Camus, C. et al. Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation. Intensive Care Med. 2006; 32(11): Covic, A. et al. Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion. Liver international. 2003; 0(23): Schmidt, LE. et al. Hemodynamic changes during a single treatment with the Molecular Adsorbent Recirculating System in patients with Acute-on-Chronic. Liver Transpl. 2001; 7(12): Sen, S. et al. Albumin dialysis reduces portal pressure acutely in patients with severe alcoholic hepatitis. J Hepatol. 2005; 43(1): Jalan, R. et al. Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis. J Hepatol. 2003; 38: Kjaergard, LL. et al. Artificial and Bioartificial Support Systems for Acute and Acute-on-Chronic Liver Failure: A Systematic Review. JAMA. 2003; 289(2): Parés, A. et al. Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2004; 99(6): Doria, C. et al. Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus. Liver Transpl. 2003; 9(4): Joannidis, M. et al. Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis. Liver Transpl. 2004; 10(1): Hessel, FP. Economic evaluation of the artificial liver support system MARS in patients with acuteon-chronic liver failure. Cost Eff Resour Alloc. 2006; 4(0): Hassanein, TI. et al. Albumin dialysis in cirrhosis with superimposed acute liver injury: possible impact of albumin dialysis on hospitalization costs. Liver International. 2003; 0(23): Mitzner SR. et al. Albumin dialysis using the molecular adsorbent recirculating system. Curr Opin Nephrol Hypertens 2001;10(6): The next step Gambro as the leading company in artificial liver support systems keeps innovating to bring you the best treatments for the management of patients suffering from liver failure.
8 Partners in care... David, Ellen, Tom, Enrico, Beatriz. They are just a handful of the hundreds of thousands of men, women and children around the world who every day rely on our products and your care to survive liver or kidney conditions and enjoy a better life. Every step we take together, every improvement in care we make, touches lives and provides new hope to José, Xiuxiu, Vladimir, Fred, Jamila... HCEN5809_ Gambro Lundia AB EDTA Edition Gambro the pioneer and leading innovator in dialysis therapy passionately committed to promoting life by advancing products, services and customer partnership within hepatic and renal care. Contact us at Gambro and MARS are registered trademarks of Gambro Lundia AB MARS FLUX is a trademark of Gambro Lundia AB, registered in the European Union and pending in the U.S. Gambro Lundia AB PO Box SE Lund Sweden Phone
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