Continuous Renal Replacement Therapy (CRRT) in Liver Failure and Other Liver Assist Devices

  • Bogdana Sabina Zoica
  • Ayse Akcan-Arikan
  • Akash DeepEmail author


Liver failure, both acute (ALF) and acute-on-chronic liver failure (ACLF), present unique challenges in critical care, especially in children. Advances in medical technology and orthotopic liver transplantation (OLT) have improved overall survival in pediatric liver failure (LF). Blood purification in the form of combined extracorporeal therapy is often necessary to support the multiple organ failure associated with a failing liver either as a bridge to spontaneous regeneration or successful liver transplantation. Different therapies using extracorporeal liver assist devices (ECLD) as well as challenges such as circuit anticoagulation will be discussed after a brief review of pathophysiology as context for extracorporeal therapy use in pediatric LF.


Liver failure Continuous renal replacement therapy Liver support Acute kidney injury 



Ammonia clearance


Acute liver failure


Acute on chronic liver failure


Acute kidney injury


Cerebral edema


Continuous renal replacement therapy


Continuous veno-venous hemofiltration


Continuous veno-venous hemodialysis


Continuous veno-venous hemodiafiltration


Extracorporeal liver assist devices


Fresh frozen plasma


Glomerular filtration rate


Hepatic encephalopathy


Hepatorenal syndrome


High volume hemofiltration


Intracranial pressure


Liver failure


Molecular absorbing recirculating system


Orthotopic liver transplantation


Regional citrate anticoagulation


Single pass albumin dialysis


Total plasma exchange


  1. 1.
    Gazzard BG, Weston MJ, Murray-Lyon IM, Flax H, Record CO, Williams R, et al. Charcoal haemoperfusion in the treatment of fulminant hepatic failure. Lancet. 1974;1(7870):1301–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Loening WE, Coovadia HM, Parent MA. Exchange transfusion in fulminant hepatic failure in children. S Afr Med J. 1974;48(4):128–30.PubMedGoogle Scholar
  3. 3.
    Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148(5):652–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Coltart I, Tranah TH, Shawcross DL. Inflammation and hepatic encephalopathy. Arch Biochem Biophys. 2013;536(2):189–96.CrossRefPubMedGoogle Scholar
  5. 5.
    Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J. Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology. 2007;46(6):1844–52.CrossRefPubMedGoogle Scholar
  6. 6.
    Wendon J, Lee W. Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. Neurocrit Care. 2008;9(1):97–102.CrossRefPubMedGoogle Scholar
  7. 7.
    Warrillow SJ. Predictions and outcomes for the critically ill patient with cirrhosis: is it time to settle on the SOFA and let jaundiced views on outcome MELD away? Crit Care Med. 2010;38(11):2259–60.CrossRefPubMedGoogle Scholar
  8. 8.
    Larsen FS, Wendon J. Prevention and management of brain edema in patients with acute liver failure. Liver Transpl. 2008;14(Suppl 2(S2)):S90–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Slack AJ, Auzinger G, Willars C, Dew T, Musto R, Corsilli D, et al. Ammonia clearance with haemofiltration in adults with liver disease. Liver Int. 2013;34(1):42–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Spinale JM, Laskin BL, Sondheimer N, Swartz SJ, Goldstein SL. High-dose continuous renal replacement therapy for neonatal hyperammonemia. Pediatr Nephrol. 2013;28(6):983–6.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ellis D, Avner ED, Starzl TE. Renal failure in children with hepatic failure undergoing liver transplantation. J Pediatr. 1986;108(3):393–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bridges BC, Askenazi DJ, Smith J, Goldstein SL. Pediatric renal replacement therapy in the intensive care unit. Blood Purif. 2012;34(2):138–48.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Stange J. Extracorporeal liver support. Organogenesis. 2011;7(1):64–73.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kreuzer M, Gähler D, Rakenius AC, Prüfe J, Jack T, Pfister E-D, et al. Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome. Pediatr Nephrol. 2015;30(12):2199–206.CrossRefPubMedGoogle Scholar
  15. 15.
    Tujios SR, Hynan LS, Vazquez MA, Larson AM, Seremba E, Sanders CM, et al. Risk factors and outcomes of acute kidney injury in patients with acute liver failure. Clin Gastroenterol Hepatol. 2015;13(2):352–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Sauer IM, Goetz M, Steffen I, Walter G, Kehr DC, Schwartlander R, et al. In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD). Hepatology. 2004;39(5):1408–14.CrossRefGoogle Scholar
  17. 17.
    Schultheiß C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care. 2012;16(4):R162.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Symons JM, Chua AN, Somers MJG, Baum MA, Bunchman TE, Benfield MR, et al. Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry. Clin J Am Soc Nephrol. 2007;2(4):732–8.CrossRefGoogle Scholar
  19. 19.
    Davenport A, Will EJ, Davison AM, Swindells S, Cohen AT, Miloszewski KJ, et al. Changes in intracranial pressure during haemofiltration in oliguric patients with grade IV hepatic encephalopathy. Nephron. 1989;53(2):142–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Sadamori H, Yagi T, Inagaki M, Shima Y, Matsuda H, Tanaka N, et al. High-flow-rate haemodiafiltration as a brain-support therapy proceeding to liver transplantation for hyperacute fulminant hepatic failure. Eur J Gastroenterol Hepatol. 2002;14(4):435–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Chevret L, Durand P, Lambert J, Essouri S, Balu L, Devictor D, et al. High-volume hemofiltration in children with acute liver failure*. Pediatr Crit Care Med. 2014;15(7):e300–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Habib M, Roberts LN, Patel RK, Wendon J, Bernal W, Arya R. Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation. Liver Int. 2014;34(5):672–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Goonasekera CD, Wang J, Bunchman TE, Deep A. Factors affecting circuit life during continuous renal replacement therapy in children with liver failure. Ther Apher Dial. 2014;19(1):16–22.CrossRefPubMedGoogle Scholar
  24. 24.
    Chadha V, Garg U, Warady BA, Alon US. Citrate clearance in children receiving continuous venovenous renal replacement therapy. Pediatr Nephrol. 2002;17(10):819–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Elhanan N, Skippen P, Nuthall G, Krahn G, Seear M. Citrate anticoagulation in pediatric continuous venovenous hemofiltration. Pediatr Nephrol. 2004;19(2):208–12.CrossRefPubMedGoogle Scholar
  26. 26.
    Musielak A, Warzywoda A, Wojtalik M, Kociński B, Kroll P, Ostalska-Nowicka D, et al. Outcomes of continuous renal replacement therapy with regional citrate anticoagulation in small children after cardiac surgery: experience and protocol from a single center. Ther Apher Dial. 2016;20(6):639–44.CrossRefPubMedGoogle Scholar
  27. 27.
    Brophy PD, Somers MJG, Baum MA, Symons JM, McAfee N, Fortenberry JD, et al. Multi-Centre evaluation of anticoagulation in patients receiving continuous renal replacement therapy (CRRT). Nephrol Dial Transplant. 2005;20(7):1416–21.CrossRefPubMedGoogle Scholar
  28. 28.
    MacLaren G, Butt W. Controversies in paediatric continuous renal replacement therapy. Intensive Care Med. 2009;35(4):596–602.CrossRefPubMedGoogle Scholar
  29. 29.
    Jacobs R, Honoré PM, Bagshaw SM, Diltoer M, Spapen HD. Citrate formulation determines filter lifespan during continuous veno-venous hemofiltration: a prospective cohort study. Blood Purif. 2015;40(3):194–202.CrossRefPubMedGoogle Scholar
  30. 30.
    Bai M, Zhou M, He L, Ma F, Li Y, Yu Y, et al. Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs. Intensive Care Med. 2015;41(12):2098–110.CrossRefPubMedGoogle Scholar
  31. 31.
    Rodriguez K, Srivaths PR, Tal L, Watson MN, Riley AA, Himes RW, et al. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure. PLoS One. 2017;12(8):e0182134.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Deep A, Stewart CE, Dhawan A, Douiri A. Effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Crit Care Med. 2016;44(10):1910–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Abe T, Kobata H, Hanba Y, Kitabata Y, Narukawa N, Hasegawa H, et al. Study of plasma exchange for liver failure: beneficial and harmful effects. Ther Apher Dial. 2004;8(3):180–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol. 2016;64(1):69–78.CrossRefPubMedGoogle Scholar
  35. 35.
    Singer AL, Olthoff KM, Kim H, Rand E, Zamir G, Shaked A. Role of plasmapheresis in the management of acute hepatic failure in children. Ann Surg. 2001;234(3):418–24.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ide K, Muguruma T, Shinohara M, Toida C, Enomoto Y, Matsumoto S, et al. Continuous veno-venous hemodiafiltration and plasma exchange in infantile acute liver failure. Pediatr Crit Care Med. 2015;16(8):e268–74.CrossRefPubMedGoogle Scholar
  37. 37.
    Stefoni S, Colì L, Bolondi L, Ruggeri G, Feliciangeli G, Piscaglia F, et al. Molecular adsorbent recirculating system (MARS) application in liver failure: clinical and hemodepurative results in 22 patients. Int J Artif Organs. 2006;29(2):207–18.CrossRefPubMedGoogle Scholar
  38. 38.
    Novelli G, Rossi M, Pretagostini R, Novelli L, Poli L, Ferretti G, et al. 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 Int. 2003;23(Suppl 3):10–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Donati G, La Manna G, Cianciolo G, Grandinetti V, Carretta E, Cappuccilli M, et al. Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up. Artif Organs. 2013;38(2):125–34.CrossRefPubMedGoogle Scholar
  40. 40.
    Bañares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57(3):1153–62.CrossRefPubMedGoogle Scholar
  41. 41.
    Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med. 2013;159(8):522–31.CrossRefPubMedGoogle Scholar
  42. 42.
    Schaefer B, Schaefer F, Engelmann G, Meyburg J, Heckert KH, Zorn M, et al. Comparison of molecular adsorbents recirculating system (MARS) dialysis with combined plasma exchange and haemodialysis in children with acute liver failure. Nephrol Dial Transplant. 2011;26(11):3633–9.CrossRefPubMedGoogle Scholar
  43. 43.
    Lexmond WS, Van Dael CML, Scheenstra R, Goorhuis JF, Sieders E, Verkade HJ, et al. Experience with molecular adsorbent recirculating system treatment in 20 children listed for high-urgency liver transplantation. Liver Transpl. 2015;21(3):369–80.CrossRefPubMedGoogle Scholar
  44. 44.
    Novelli G, Rossi M, Morabito V, Pugliese F, Ruberto F, Perrella SM, et al. Pediatric acute liver failure with molecular adsorbent recirculating system treatment. Transplant Proc. 2008;40(6):1921–4.CrossRefPubMedGoogle Scholar
  45. 45.
    Schaefer B, Ujszaszi A, Schaefer S, Heckert KH, Schaefer F, Schmitt CP. Safety and efficacy of tandem hemodialysis and plasma exchange in children. Clin J Am Soc Nephrol. 2014;9(9):1563–70.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Sponholz C, Matthes K, Rupp D, Backaus W, Klammt S, Karailieva D, et al. Molecular adsorbent recirculating system and single-pass albumin dialysis in liver failure—a prospective, randomised crossover study. Crit Care. 2016;20(1):2.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ringe H, Varnholt V, Zimmering M, Luck W, Gratopp A, König K, et al. Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure. Pediatr Crit Care Med. 2011;12(3):257–64.CrossRefPubMedGoogle Scholar
  48. 48.
    Kortgen A, Rauchfuss F, Götz M, Settmacher U, Bauer M, Sponholz C. Albumin dialysis in liver failure: comparison of molecular adsorbent recirculating system and single pass albumin dialysis--a retrospective analysis. Ther Apher Dial. 2009;13(5):419–25.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Bogdana Sabina Zoica
    • 1
  • Ayse Akcan-Arikan
    • 2
    • 3
  • Akash Deep
    • 1
    Email author
  1. 1.Pediatric Intensive Care, King’s College HospitalLondonUK
  2. 2.Department of PediatricsSections of Critical Care and Nephrology, Texas Children’s HospitalHoustonUSA
  3. 3.Critical Care Nephrology, Texas Children’s HospitalHoustonUSA

Personalised recommendations