Liver Transplantation From Uncontrolled DCD Donors

  • Amelia J. Hessheimer
  • Alba Torroella
  • Constantino FondevilaEmail author


Uncontrolled donation after circulatory death (uDCD) donors suffer sudden and unanticipated cardiac arrest, typically outside the hospital setting. After advanced cardiopulmonary resuscitation has been attempted and determined to be unsuccessful, uDCD may be considered. At present, all programs recovering and transplanting uDCD livers rely on postmortem normothermic regional perfusion (NRP) to restore the flow of oxygenated blood following declaration of death. In this chapter, we discuss different aspects related to liver transplantation uDCD donors, including logistical and ethical issues surrounding the uDCD process, the use of NRP, graft and recipient selection criteria, perioperative recipient management, and post-transplantation outcomes that have been reported to date. We aim to demonstrate that, while uDCD is complex and the yield of livers for transplantation remains relatively low, it is nonetheless a viable alternative to more standard forms of liver donation and one that may be able to be expanded in the coming years through advances in both donor maintenance and ex situ organ preservation.


Extended criteria donor Ischemia reperfusion injury Marginal graft Normothermic regional perfusion Warm ischemia 


  1. 1.
    Royal Decree 1723/2012, December 28, 2012, Annex I, Section 3: Diagnosis of death based on circulatory and respiratory criteria. URL: 2012.
  2. 2.
    Aguilar A, Alvarez-Vijande R, Capdevila S, Alcoberro J, Alcaraz A. Antioxidant patterns (superoxide dismutase, glutathione reductase, and glutathione peroxidase) in kidneys from non-heart-beating-donors: experimental study. Transplant Proc. 2007;39(1):249–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Blasi A, Hessheimer AJ, Beltran J, Pereira A, Fernandez J, Balust J, Martinez-Palli G, Fuster J, Navasa M, Garcia-Valdecasas JC, Taura P, Fondevila C. Liver transplant from unexpected donation after circulatory determination of death donors: a challenge in perioperative management. Am J Transplant. 2016;16(6):1901–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Casavilla A, Ramirez C, Shapiro R, Nghiem D, Miracle K, Bronsther O, Randhawa P, Broznick B, Fung JJ, Starzl T. Experience with liver and kidney allografts from non-heart-beating donors. Transplantation. 1995;59(2):197–203.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Croome KP, Lee DD, Keaveny AP, Taner CB. Improving national results in liver transplantation using grafts from donation after cardiac death donors. Transplantation. 2016 Dec;100(12):2640–7.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Das S, Maggio AJ, Sacks SA, Smith RB, Kaufman JJ. Effects of preliminary normothermic flushing on hypothermic renal preservation. Urology. 1979;14(5):505–8.PubMedCrossRefGoogle Scholar
  7. 7.
    De Carlis R, Di SS, Lauterio A, Botta F, Ferla F, Andorno E, Bagnardi V, De CL. Liver grafts from donors after circulatory death on regional perfusion with extended warm ischemia compared with donors after brain death. Liver Transpl. 2018;24(11):1523–35.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Fondevila C, Hessheimer AJ, Flores E, Ruiz A, Mestres N, Calatayud D, Paredes D, Rodriguez C, Fuster J, Navasa M, Rimola A, Taura P, Garcia-Valdecasas JC. Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation. Am J Transplant. 2012;12(1):162–70.PubMedCrossRefGoogle Scholar
  9. 9.
    Fondevila C, Hessheimer AJ, Ruiz A, Calatayud D, Ferrer J, Charco R, Fuster J, Navasa M, Rimola A, Taura P, Gines P, Manyalich M, Garcia-Valdecasas JC. Liver transplant using donors after unexpected cardiac death: novel preservation protocol and acceptance criteria. Am J Transplant. 2007;7(7):1849–55.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Garcia-Valdecasas JC, Tabet J, Valero R, Taura P, Rull R, Garcia F, Montserrat E, Gonzalez FX, Ordi J, Beltran J, Lopez-Boado MA, Deulofeu R, Angas J, Cifuentes A, Visa J. Liver conditioning after cardiac arrest: the use of normothermic recirculation in an experimental animal model. Transpl Int. 1998;11(6):424–32.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Gonzalez FX, Garcia-Valdecasas JC, Lopez-Boado MA, Tabet J, Net M, Grande L, Cifuentes A, Rull R, Valero R, Beltran J, Elena M, Cabrer C, Palacin J, Visa J. Adenine nucleotide liver tissue concentrations from non-heart-beating donor pigs and organ viability after liver transplantation. Transplant Proc. 1997;29(8):3480–1.PubMedCrossRefGoogle Scholar
  12. 12.
    Hagness M, Foss S, Sorensen DW, Syversen T, Bakkan PA, Dahl T, Fiane A, Line P. Liver transplant after normothermic regional perfusion from controlled donors after circulatory death: the norwegian experience. Transplant Proc. 2019;51(2):475–8.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Harvey PR, Iu S, McKeown CM, Petrunka CN, Ilson RG, Strasberg SM. Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. Transplantation. 1988;45(6):1016–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Hessheimer AJ, Garcia-Valdecasas JC, Fondevila C. Abdominal regional in-situ perfusion in donation after circulatory determination of death donors. Curr Opin Organ Transplant. 2016;21(3):322–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Hong JC, Yersiz H, Kositamongkol P, Xia VW, Kaldas FM, Petrowsky H, Farmer DG, Lipshutz G, Markovic D, Hiatt JR, Busuttil RW. Liver transplantation using organ donation after cardiac death: a clinical predictive index for graft failure-free survival. Arch Surg. 2011;146(9):1017–23.CrossRefGoogle Scholar
  16. 16.
    Jiménez-Romero C, Manrique A, Calvo J, Caso O, Marcacuzco A, García-Sesma A, Abradelo M, Nutu A, García-Conde M, San Juan R, Justo I. Liver transplantation using uncontrolled donors after circulatory death: a 10-year single-center experience. Transplantation. (In press). 2019;103:2497.PubMedCrossRefGoogle Scholar
  17. 17.
    Kerforne T, Allain G, Giraud S, Bon D, Ameteau V, Couturier P, Hebrard W, Danion J, Goujon JM, Thuillier R, Hauet T, Barrou B, Jayle C. Defining the optimal duration for normothermic regional perfusion in the kidney donor: a porcine preclinical study. Am J Transplant. 2019;19(3):737–51.PubMedCrossRefGoogle Scholar
  18. 18.
    Khorsandi SE, Giorgakis E, Vilca-Melendez H, O'Grady J, Heneghan M, Aluvihare V, Suddle A, Agarwal K, Menon K, Prachalias A, Srinivasan P, Rela M, Jassem W, Heaton N. Developing a donation after cardiac death risk index for adult and pediatric liver transplantation. World J Transplant. 2017;7(3):203–12.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kimber RM, Metcalfe MS, White SA, Nicholson ML. Use of non-heart-beating donors in renal transplantation. Postgrad Med J. 2001;77(913):681–5.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Kreibich M, Trummer G, Beyersdorf F, Scherer C, Forster K, Taunyane I, Benk C. Improved outcome in an animal model of prolonged cardiac arrest through pulsatile high pressure controlled automated reperfusion of the whole body. Artif Organ. 2018;42(10):992–1000.CrossRefGoogle Scholar
  21. 21.
    Laing RW, BoteonYL, Kirkham A, Perera MTPR, Attard J, Barton D, Curbishley S, Neil DA., Hübscher SG, Muiesan P, Isaac JR, Roberts KJ, Abradelo M, Ferguson J, Cilliers H, Bion J, Morris C, Friend PJ, Yap C, Afford SC, Mergental H, Mizra DF. Transplantation of discarded livers following viability testing with normothermic machine perfusion: The VITTAL (VIability Testing and Transplantation of mArginal Livers) trial outcomes. Transplantation [Supplement]. 2019.Google Scholar
  22. 22.
    Link MS, Berkow LC, Kudenchuk PJ, Halperin HR, Hess EP, Moitra VK, Neumar RW, O'Neil BJ, Paxton JH, Silvers SM, White RD, Yannopoulos D, Donnino MW. Part 7: adult advanced cardiovascular life support: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S444–64.PubMedCrossRefGoogle Scholar
  23. 23.
    Lomero M, Gardiner D, Coll E, Haase-Kromwijk B, Procaccio F, Immer F, Gabbasova L, Antoine C, Jushinskis J, Lynch N, Foss S, Bolotinha C, Ashkenazi T, Colenbie L, Zuckermann A, Adamec M, Czerwinski J, Karciauskaite S, López-Fraga M, Dóminguez-Gil B. Donation after circulatory death today: an updated overview of the European landscape. Transpl Int. 2019. (In press).Google Scholar
  24. 24.
    Mergental H, Perera MT, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson BT, Cilliers H, Neil DA, Hubscher SG, Afford SC, Mirza DF. Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transpl. 2016;16(11):3235–45.CrossRefGoogle Scholar
  25. 25.
    Net M, Valero R, Almenara R, Barros P, Capdevila L, Lopez-Boado MA, Ruiz A, Sanchez-Crivaro F, Miquel R, Deulofeu R, Taura P, Manyalich M, Garcia-Valdecasas JC. The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation. Am J Transpl. 2005;5(10):2385–92.CrossRefGoogle Scholar
  26. 26.
    Net M, Valero R, Almenara R, Deulofeu R, Lopez-Boado MA, Capdevila L, Barros P, Bombi JA, Agusti M, Adalia R, Ruiz A, Arce Y, Manyalich M, Garcia-Valdecasas JC. Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors. Transplantation. 2003;75(12):1970–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Net M, Valero R, Almenara R, Rull R, Gonzalez FJ, Taura P, Lopez-Boado MA, Deulofeu R, Elena M, Capdevila L, Cabrer C, Visa J, Garcia-Valdecasas JC. Hepatic xanthine levels as viability predictor of livers procured from non-heart-beating donor pigs. Transplantation. 2001;71(9):1232–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Organización Nacional de Trasplantes 2012, Donación en Asistolia en España: Situación Actual y Recomendaciones. URL:
  29. 29.
    Organización Nacional de Trasplantes 2015, Protocolo Nacional de Donación y Trasplante Hepático en Donación en Asistolia Controlada. URL:
  30. 30.
    Organización Nacional de Trasplantes 2017, Informe de Actividad de Donación y Trasplante de Donantes en Asistolia. URL:
  31. 31.
    Otero A, Gomez-Gutierrez M, Suarez F, Arnal F, Fernandez-Garcia A, Aguirrezabalaga J, Garcia-Buitron J, Alvarez J, Manez R. Liver transplantation from Maastricht category 2 non-heart-beating donors. Transplantation. 2003;76(7):1068–73.PubMedCrossRefGoogle Scholar
  32. 32.
    Pavel MC, Reyner E, Fuster J, Garcia-Valdecasas JC. Liver transplantation from type II donation after cardiac death donor with normothermic regional perfusion and normothermic machine perfusion. Cir Esp. 2018;96(8):508–13.PubMedCrossRefGoogle Scholar
  33. 33.
    Reznik O, Skvortsov A, Loginov I, Ananyev A, Bagnenko S, Moysyuk Y. Kidney from uncontrolled donors after cardiac death with one hour warm ischemic time: resuscitation by extracorporal normothermic abdominal perfusion "in situ" by leukocytes-free oxygenated blood. Clin Transplant. 2011;25(4):511–6.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Savier E, Dondero F, Vibert E, Eyraud D, Brisson H, Riou B, Fieux F, Naili-Kortaia S, Castaing D, Rouby JJ, Langeron O, Dokmak S, Hannoun L, Vaillant JC. First experience of liver transplantation with type 2 donation after cardiac death in France. Liver Transpl. 2015;21(5):631–43.PubMedCrossRefGoogle Scholar
  35. 35.
    Schlegel A, Kalisvaart M, Scalera I, Laing RW, Mergental H, Mirza DF, Perera T, Isaac J, Dutkowski P, Muiesan P. The UK DCD risk score: a new proposal to define futility in donation-after-circulatory-death liver transplantation. J Hepatol. 2018;68(3):456–64.CrossRefGoogle Scholar
  36. 36.
    Soar J, Nolan JP, Bottiger BW, Perkins GD, Lott C, Carli P, Pellis T, Sandroni C, Skrifvars MB, Smith GB, Sunde K, Deakin CD. European resuscitation council guidelines for resuscitation 2015: section 3. Adult advanced life support. Resuscitation. 2015;95:100–47.PubMedCrossRefGoogle Scholar
  37. 37.
    Suarez F, Otero A, Solla M, Arnal F, Lorenzo MJ, Marini M, Vazquez-Iglesias JL, Gomez M. Biliary complications after liver transplantation from Maastricht category-2 non-heart-beating donors. Transplantation. 2008;85(1):9–14.PubMedCrossRefGoogle Scholar
  38. 38.
    Taunyane IC, Benk C, Beyersdorf F, Foerster K, Cristina SH, Wittmann K, Mader I, Doostkam S, Heilmann C, Trummer G. Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes. Eur J Cardiothorac Surg. 2016;50(6):1025–34.PubMedCrossRefGoogle Scholar
  39. 39.
    Thuong M, Ruiz A, Evrard P, Kuiper M, Boffa C, Akhtar MZ, Neuberger J, Ploeg R. New classification of donation after circulatory death donors definitions and terminology. Transpl.Int. 2016;29(7):749–59.PubMedCrossRefGoogle Scholar
  40. 40.
    Trummer G, Benk C, Beyersdorf F. Controlled automated reperfusion of the whole body after cardiac arrest. J Thorac Dis. 2019;11(Suppl 10):S1464–70.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Tuttle-Newhall JE, Krishnan SM, Levy MF, McBride V, Orlowski JP, Sung RS. Organ donation and utilization in the United States: 1998-2007. Am.J.Transplant. 2009;9(4 Pt 2):879–93.PubMedCrossRefGoogle Scholar
  42. 42.
    Watson CJE, Kosmoliaptsis V, Pley C, Randle L, Fear C, Crick K, Gimson AE, Allison M, Upponi S, Brais R, Jochmans I, Butler AJ. Observations on the ex situ perfusion of livers for transplantation. Am.J.Transplant. 2018;18(8):2005–20.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Amelia J. Hessheimer
    • 1
  • Alba Torroella
    • 1
  • Constantino Fondevila
    • 1
    Email author
  1. 1.Department of Hepatopancreatobiliary Surgery and TransplantationHospital Clínic, IDIBAPS, CIBEREHD, University of BarcelonaBarcelonaSpain

Personalised recommendations