Extrakorporale Blutreinigung im schweren Leberversagen mit der Albumindialyse MARS® - Einfluss auf intensivmedizinisch relevante Parameter

Zusammenfassung

Klinische Studien zum Einsatz von extrakorporalen Leberersatzverfahren werden seit über 50 Jahren durchgeführt. Dabei kamen sowohl die Standard-Blutreinigungstechniken wie die Dialyse, Adsorption, Hämo- und Plasmafiltration als auch Bioreaktor-basierte Ansätze unter Verwendung von Leberzellen oder -geweben zum Einsatz. Die klinischen Erfahrungen beschränken sich dabei allerdings meist auf die Nutzung im akuten Leberversagen. Seit 1993 steht mit dem Molecular Adsorbent Recirculating System (MARS®) ein Verfahren zur Verfügung, das die Techniken von Dialyse, Filtration und Adsorption in einem biokompatiblen Ansatz vereint. Humanes Serum Albumin (HSA) wird dabei als selektiver molekularer Adsorber eingesetzt, der gezielt eiweißgebundene Substanzen, wie etwa Gallensäuren oder Bilirubin, binden kann. Die Anhäufung von Substanzen dieser Gruppe kann wesentlich zum Unterhalt und zur Verstärkung von Organdysfunktionen im Leberversagen beitragen. Sie werden unter anderem mit der Entstehung bzw. Verschlechterung der hyperdynamen hypotonen Kreislaufdysregulation, der hepatischen Enzephalopathie, dem hepatorenalen Syndrom, eingeschränkter hepatischer Proteinsynthese und starkem Juckreiz beim Leberversagen in Zusammenhang gebracht. Das HSA übernimmt die Giftstoffe vom Patientenblut und durchläuft eine, räumlich vom Blut getrennte, Entgiftungsstrecke (eine Bicarbonatdialyse, zwei Adsorber), um dann erneut zum Patientenblut zurückzufließen. Bis heute wurden über 4000 Patienten mit Leberversagen mit mehr als 16 000 Einzelbehandlungen therapiert. Damit handelt es sich beim MARS®-Verfahren um das am häufigsten klinisch eingesetzte Leberunterstützungssystem. Neben akuten Leberversagen wurden vor allem akut dekompensierte chronische Lebererkrankungen (Acute-on-Chronic Liver Failure, ACLF) behandelt. Der Einfluss auf intensivmedizinisch relevante Parameter durch die extrakorporale Behandlung wird im Zusammenhang mit den Besonderheiten eines Patienten mit einem Leberversagen (Infektanfälligkeit, atypischer Infektverlauf, Gerinnungsstörungen mit Blutungsneigung) diskutiert.

Abstract

Extracorporeal liver support methods have been tested for over 50 years now. Standard techniques of blood purification like dialysis, adsorption, hemo- and plasmafiltration as well as bioreactor-based approaches using liver cells or tissues have been used. Most clinical experience, however, is limited to use in acute liver failure (ALF). Since 1993, the Molecular Adsorbent Recirculating System (MARS®) has been used clinically - a system that combines dialysis, filtration and adsorption in a biocompatible method. Human serum albumin (HSA) acts as a selective molecular adsorbent binding protein-bound compounds like bile acids or bilirubin. These substances can contribute to the maintenance or even further aggravation of liver failure. They are linked with the pathogenesis of hyperdynamic hypotonic circulation, hepatic encephalopathy, hepatorenal syndrome, impaired hepatic protein synthesis, and intractable pruritus seen in chronic liver failure. HSA takes over the toxic substances from a patient"s blood and passes through a remote detoxification process including bicarbonate-dialysis and a two-step adsorption. It is then recirculated in the patient's blood. Up to today, more than 4000 patients have been treated in approximately 16 000 single sessions. Thus, MARS® represents the most frequently used liver support method at the present time. In addition to ALF, mainly acute decompensations of chronic liver failures (ACLF) have been treated. The impact of the extracorporeal treatment on relevant medical parameters of intensive care medicine is discussed with regard to the specific situation of the liver-failure patient (susceptibility to infection, atypical picture and course of infection, coagulation disorders and bleeding tendencies).

Schlüsselwörter

Leberschaden · Bilirubin · Gallensäuren · Albumin · Albumindialyse · Leberersatzverfahren

Key words

Hepatic failure · bilirubin · bile acids · albumin · albumin dialysis · liver support methods

Literatur

• 1 Allen J W, Hassanein T, Bhatia S N. Advances in bioartificial liver devices.  Hepatology. 2001;  34 447-455
• 2 Awad S S, Sawada S, Soldes O S, Rich P B, Klein R, Alarcon W H, Wang S C, Bartlett R H. Can the clearance of tumor necrosis factor alpha and interleukin 6 be enhanced using an albumin dialysate hemodiafiltration system?.  ASAIO J. 1999;  45 47-49
• 3 Awad S S, Swaniker F, Magee J, Punch J, Bartlett R H. Results of a phase I trial evaluating a liver support device utilizing albumin dialysis.  Surgery. 2001;  130 354-362
• 4 Banayosy A, Kizner L, Schueler V, Bergmeier S, Cobaugh D, Koerfer R. Role of MARS in patients suffering from hypoxic liver failure following cardiogenic shock after cardiac surgery (Abstract).  J Hepatol. 2003;  38 (Suppl 2) 35
• 5 Campli C D, Gaspari R, Mignani V, Stifano G, Santoliquido A, Verme L Z, Proietti R, Pola P, Silveri N G, Gasbarrini G, Gasbarrini A. Successful MARS treatment in severe cholestatic patients with acute on chronic liver failure.  Artif Organs. 2003;  27 565-569
• 6 Catalina M V, Barrio J, Anaya F, Salcedo M, Rincon D, Clemente G, Banares R. Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure.  Liver Internat. 2003;  23 (Suppl 3) 39-43
• 7 Chen S, Zhang L, Shi Y, Yang X, Wang M. Molecular adsorbent recirculating system: clinical experience in patients with liver failure based on hepatitis B in China.  Liver. 2002;  22 (Suppl 2) 48-51
• 8 Covic A, Goldsmith D J, Gusbeth-Tatomir P, Volovat C, Dimitriu A G, Cristogel F, Bizo A. Successful use of Molecular Adsorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion.  Liver Internat. 2003;  23 (Suppl 3) 21-27
• 9 Davenport S. Artificial hepatic support: where are we now?.  Blood Purif. 2001;  19 1-3
• 10 Doria C, Mandala L, Smith J, Vitale C H, Lauro A, Gruttadauria S, Marino I R, Foglieni C S, Magnone M, Scott V L. Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus.  Liver Transpl. 2003;  9 437-443
• 11 Guo L M, Liu J Y, Xu D Z, Li B S, Han H, Wang L H, Zhang W Y, Lu L H, Guo X, Sun F X, Zhang H Y, Liu X D, Zhang J P, Yao Y, He Z P, Wang M M. Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome.  Liver Internat. 2003;  23 (Suppl 3) 16-20
• 12 Hassanein T, Oliver D, Stange J, Steiner C. Albumin dialysis in cirrhosis with superimposed acute liver injury: possible impact of albumin dialysis on hospitalization costs.  Liver Internat. 2003;  23 (Suppl 3) 61-65
• 13 Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M, Klammt S, Loehr M, Liebe S, Mitzner S, Schmidt R, Stange J. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.  Hepatology. 2002;  36 949-958
• 14 Hessel F P, Mitzner S R, Rief J, Guellstorff B, Steiner S, Wasem J. Economic evaluation and 1-year survival analysis of MARS in patients with alcoholic liver disease.  Liver Internat. 2003;  23 Suppl 3 66-72
• 15 Hommann M, Kasakow L B, Geoghegan J, Kornberg A, Schotte U, Fuchs D, Hermann J, Zintl F, Scheele J. Application of MARS artificial liver support as bridging therapy before split liver retransplantation in a 15-month-old child. Pediatr.  Tranplant. 2002;  6 340-343
• 16 Huster D, Schubert C, Berr F, Mossner J, Caca K. Rofecoxib-induced cholestatic hepatitis: treatment with molecular adsorbent recycling system (MARS).  J Hepatol. 2002;  37 413-414
• 17 Ichai P, Samuel D. Extracorporeal liver support with MARS in liver failure: has it a role in the treatment of severe alcoholic hepatitis?.  J Hepatol. 2003;  38 104-106
• 18 Isoniemi H. Current indications for albumin dialysis: Acute hepatic failure. 4th International Symposium on Albumin Dialysis in Liver Disease, 6. - 8. September 2002, Book of Abstracts. Rostock; 2002 21
• 19 Jalan R, Sen S, Steiner C, Kapoor D, Alisa A, Williams R. Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis.  J Hepatol. 2003;  38 24-31
• 20 Javouhey E, Collard L, Cochat P, Floret D. Bridge to liver transplantation using extracorporeal albumin dialysis: preliminary results in children (Abstract).  Pediatr Transplant. 2003;  7 (Suppl 4) 121
• 21 Kamath P S, Wiesner R H, Malinchoc M, Kremers W, Therneau T M, Kosberg C L, D'Amico G, Dickson E R, Kim W R. A model to predict survival in patients with end-stage liver disease.  Hepatology. 2001;  33 464-470
• 22 Kiley J E, Welch H F, Pender J C, Welch C S. Removal of blood ammonia by hemodialysis.  Proc Soc Exp Biol Med. 1956;  91 489-490
• 23 Kjaergard L L, Liu J, Als-Nielsen B, Gluud C. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review.  JAMA. 2003;  289 217-222
• 24 Klammt S, Stange J, Mitzner S R, Peszynski P, Peters E, Liebe S. Extracorporeal liver support by recirculating albumin dialysis: analysing the effect of the first clinically used generation of the MARSystem.  Liver. 2002;  22 (Suppl 2) 30-34
• 25 Koivusalo A M, Yildirim Y, Vakkuri A, Lindgren L, Hockerstedt K, Isoniemi H. Experience with albumin dialysis in five patients with severe overdoses of paracetamol.  Acta Anaesthesiol Scand. 2003;  47 1145-1150
• 26 Kramer L, Gendo A, Madl C, Ferrara I, Funk G, Schenk P, Sunder-Plassmann G, Hörl W H. Biocompatibility of a cuprophane charcoal-based detoxification device in cirrhotic patients with hepatic encephalopathy.  Am J Kidney Dis. 2000;  36 1193-1200
• 27 Loock J, Treichel U, Gerken G, Malago M, Broelsch C E, Phillip T, Heemann U. Treatment of split-liver recipients with poor graft function by albumin dialysis (MARS).  Z Gastroenterol. 2001;  39 (Suppl 2) 18
• 28 Manz T, Ochs A, Bisse E, Strey C, Grotz W. Liver support - a task for nephrologists? Extracorporeal treatment of a patient with fulminant Wilson crisis.  Blood Purif. 2003;  21 232-236
• 29 McIntyre C W, Fluck R J, Freeman J G, Lambie S H. Characterization of treatment dose delivered by albumin dialysis in the treatment of acute renal failure associated with severe hepatic dysfunction.  Clin Nephrol. 2002;  58 376-383
• 30 McIntyre C W, Fluck R J, Freeman J G, Lambie S H. Use of albumin dialysis in the treatment of hepatic and renal dysfunction due to paracetamol intoxication.  Nephrol Dial Transplant. 2002;  17 316-317
• 31 Mitzner S, Stange J. Cell-free artificial liver support: a critical review. In: Körner MM, Körfer R (eds) Current aspects and concepts of nursing, coordinating, bridging and rehabilitation in organ transplantation. Amsterdam; Elsevier 1995: 81-88
• 32 Mitzner S, Stange J, Klammt S, Freytag J, Peszynski P, Loock J, Hickstein H, Korten G, Schmidt R, Henschel J, Schulz M, Lohr M, Liebe S, Schareck W, Hopt U T. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial.  Liver Transpl. 2000;  6 277-286
• 33 Mitzner S R, Stange J, Klammt S, Peszynski P, Schmidt R. Albumin dialysis using the molecular adsorbent recirculating system.  Curr Opin Nephrol Hypertens. 2001;  10 777-783
• 34 Mitzner S, Stange J, Klammt S, Peszynski P, Schmidt R, Nöldge-Schomburg G. Extracorporeal detoxification using the molecular adsorbent recirculating system for critically ill patients with liver failure.  J Amer Soc Nephrol. 2001;  12 (Suppl 17) S75-S82
• 35 Mitzner S, Loock J, Peszynski P, Klammt S, Majcher-Peszynska J, Gramowski A, Stange J, Schmidt R. Improvement in central nervous system functions during treatment of liver failure with albumin dialysis MARS - a review of clinical, biochemical, and electrophysiological data.  Metab Brain Dis. 2002;  17 463-475
• 36 Mullhaupt B, Kullak-Ublick G A, Ambuhl P M, Stocker R, Renner E L. Successful use of the Molecular Adsorbent Recirculating System (MARS) in a patient with primary biliary cirrhosis (PBC) and treatment refractory pruritus.  Hepatol Res. 2003;  25 442-446
• 37 Novelli G, Rossi M, Pretagostini R, Novelli L, Poli L, Ferretti G, Iappelli M, Berloco P, Cortesini R. A 3-year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color doppler US evaluation of cerebral perfusion.  Liver Internat. 2003;  23 (Suppl 3) 10-15
• 38 O'Grady J G, Gimson A E, O'Brien C J, Pucknell A, Hughes R D, Williams R. Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure.  Gastroenterology. 1988;  94 1186-1192
• 39 Pares A, Cisneros L, Salmeron J M, Mas A, Torras A, Caballeria J, Rodes J. The Molecular Adsorbent Recirculating System (MARS) improves systemic hemodynamics and hepatic encephalopathy in patients with severe alcoholic hepatitis.  J Hepatol. 2002;  36 (Suppl 1) 541
• 40 Parés A, Cisneros L, Salmerón J M, Caballería L, Mas A, Torras A, Rodés J. Extracorporeal albumin dialysis: A procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis.  Amer J Gastroenterol. 2004;  99 1105-1110
• 41 Peszynski P, Klammt S, Peters E, Mitzner S, Stange J, Schmidt R. Albumin dialysis: single pass vs. recirculation (MARS).  Liver. 2002;  22 (Suppl 2) 40-42
• 42 Prokurat S, Grenda R, Lipowski D, Kalicinski P, Migdal M. MARS procedure as a bridge to combined liver-kidney transplantation in severe chromium-copper acute intoxication: a paediatric case report.  Liver. 2002;  22 (Suppl 2) 76-77
• 43 Rifai K, Ernst T, Kretschmer U, Bahr M J, Schneider A, Hafer C, Haller H, Manns M P, Fliser D. Prometheus - a new extracorporeal system for the treatment of liver failure.  J Hepatol. 2003;  39 984-990
• 44 Schachschal G, Morgera S, Kupferling S, Schmidt H H, Lochs H. MARS dialysis in the state of chronic rejection in a liver transplant recipient.  Am J Gastroenterol. 2002;  97 1059-1060
• 45 Schmidt L E, Svendsen L B, Sorensen V R, Hansen B A, Larsen F S. Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure.  Liver Transpl. 2001;  7 709-712
• 46 Schmidt L E, Sorensen V R, Svendsen L B, Hansen B A, Larsen F S. Hemodynamic changes during a single treatment with the molecular adsorbents recirculating system in patients with acute-on-chronic liver failure.  Liver Transpl. 2001;  7 1034-1039
• 47 Schmidt L E, Wang L P, Hansen B A, Larsen F S. Systemic hemodynamic effects of treatment with the Molecular Adsorbents Recirculating System in patients with hyperacute liver failure: a prospective, controlled trial.  Liver Transpl. 2003;  9 290-297
• 48 Sen S, Felldin M, Steiner C, Larsson B, Gillett G T, Olausson M, Williams R, Jalan R. Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson's disease.  Liver Transpl. 2002;  8 962-967
• 49 Sen S, Mookerjee R P, Davies N A, Williams R, Jalan R. Review article: the molecular adsorbents recirculating system (MARS) in liver failure.  Aliment Pharmacol Ther. 2002;  16 (Suppl 5) 32-38
• 50 Sen S, Williams R, Jalan R. The pathophysiological basis of acute-on-chronic liver failure.  Liver. 2002;  22 (Suppl 2) 5-13
• 51 Sen S, Ratnaraj N, Davies N A, Mookerjee R P, Cooper C E, Patsalos P N, Williams R, Jalan R. Treatment of phenytoin toxicity by the Molecular Adsorbents Recirculating System (MARS).  Epilepsia. 2003;  44 265-267
• 52 Sen S, Rose C, Ytrebo L M, Davies N A, Nedredal G I, Drevland S S, Kjonno M, Williams R, Butterworth R, Revhaug A, Jalan R. Albumin dialysis reduces brain water and intracranial pressure in acute liver failure: a randomized controlled study in a pig model (Abstract).  Hepatology. 2003;  34 (Suppl 1) 540A
• 53 Siewert-Delle A, Henriksson B A, Bäckman L. Albumin dialysis with the MARS (Molecular adsorbent Recirculating system) for a patient with acute liver failure due to paracetamol intoxication: a case report. (Abstract).  Z Gastroenterol. 2001;  39 (Suppl 2) 48
• 54 Sorkine P, Ben Abraham R, Szold O. Liver support systems. In: Vincent JL (ed) 2001 Yearbook of intensive care and emergency medicine. Berlin; Springer 2001: 619-627
• 55 Sorkine P, Ben Abraham R, Szold O, Biderman P, Kidron A, Merchav H, Brill S, Oren R. Role of the molecular adsorbent recycling system (MARS) in the treatment of patients with acute exacerbation of chronic liver failure.  Crit Care Med. 2001;  29 1332-1336
• 56 Stange J, Mitzner S, Ramlow W, Gliesche T, Hickstein H, Schmidt R. A new procedure for the removal of protein bound drugs and toxins.  ASAIO J. 1993;  39 M621-M625
• 57 Stange J, Mitzner S, Klammt S, Freytag J, Peszynski P, Loock J, Hickstein H, Korten G, Schmidt R, Hentschel J, Schulz M, Löhr M, Liebe S, Schareck W, Hopt U T. Liver support by extracorporeal blood purification: a clinical observation.  Liver Transpl. 2000;  6 603-613
• 58 Steiner C, Mitzner S. Experiences with MARS liver support therapy in liver failure: analysis of 176 patients of the International MARS Registry.  Liver. 2002;  22 (Suppl 2) 20-25
• 59 Stockmann H B, Hiemstra C A, Marquet R L, Ijzermans J NM. Extracorporeal perfusion for the treatment of acute liver failure.  Ann Surg. 2000;  231 460-470
• 60 Voiculescu M, Ioanitescu S, Rusu E, Micu D, Mihaila M, Micu L. Successful application of MARS therapy in a 7 year-old patient with hepatic chronic rejection and severe cholestatic syndrome.  Rom J Gastroenterol. 2002;  11 135-140
• 61 Wehler M, Kokoska J, Reulbach U, Hahn E G, Strauss R. Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems.  Hepatology. 2001;  34 255-261
• 62 Zakaria N, Wendon J, Creamer D, Heaton N, Devlin J. Albumin dialysis (MARS device) relieves cholestatic pruritus in a dramatic but non-sustained manner.  Hepatology. 2001;  34 550A