Sequential Use of Normothermic Regional and Ex Situ Machine Perfusion in Donation After Circulatory Death Liver Transplant

Davide Ghinolfi, Daniele Dondossola, Erion Rreka, Caterina Lonati, Daniele Pezzati, Andrea Cacciatoinsilla, Alessia Kersik, Chiara Lazzeri, Alberto Zanella, Adriano Peris, Marco Maggioni, Giandomenico Biancofiore, Paolo Reggiani, Riccardo Morganti, Paolo De Simone, Giorgio Rossi, Davide Ghinolfi, Daniele Dondossola, Erion Rreka, Caterina Lonati, Daniele Pezzati, Andrea Cacciatoinsilla, Alessia Kersik, Chiara Lazzeri, Alberto Zanella, Adriano Peris, Marco Maggioni, Giandomenico Biancofiore, Paolo Reggiani, Riccardo Morganti, Paolo De Simone, Giorgio Rossi

Abstract

In Italy, 20 minutes of a continuous flat line on an electrocardiogram are required for declaration of death. In the setting of donation after circulatory death (DCD), prolonged warm ischemia time prompted the introduction of abdominal normothermic regional perfusion (NRP) followed by postprocurement ex situ machine perfusion (MP). This is a retrospective review of DCD liver transplantations (LTs) performed at 2 centers using sequential NRP and ex situ MP. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, and 11 (32.4%) were discarded based on NRP parameters (n = 1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n = 9, 26.5%), or severe macroangiopathy at back-table evaluation (n = 1, 3.0%). A total of 20 grafts (58.8%; 11 uncontrolled DCDs, 9 controlled DCDs) were considered eligible for LT, procured and perfused ex situ (9 normothermic and 11 dual hypothermic MPs). In total, 18 (52.9%; 11 uncontrolled) livers were eventually transplanted. Median (interquartile range) no-flow time was 32.5 (30-39) minutes, whereas median functional warm ischemia time was 52.5 (47-74) minutes (controlled DCD), and median low-flow time was 112 minutes (105-129 minutes; uncontrolled DCD). There was no primary nonfunction, while postreperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury occurred in 5 (28%). After a median follow-up of 15.1 (9.5-22.3) months, 1 case of ischemic-type biliary lesions and 1 patient death were reported. DCD LT is feasible even with the 20-minute no-touch rule. Strict NRP and ex situ MP selection criteria are needed to optimize postoperative results.

Copyright © 2020 by the American Association for the Study of Liver Diseases.

References

    1. Jadlowiec CC, Taner T. Liver transplantation: current status and challenges. World J Gastroenterol 2016;22:4438-4445.
    1. Schlegel A, Kalisvaart M, Scalera I, Laing RW, Mergental H, Mirza DF, et al. The UK DCD Risk Score: a new proposal to define futility in donation-after-circulatory-death liver transplantation. J Hepatol 2018;68:456-464.
    1. Neyrinck A, Van Raemdonck D, Monbaliu D. Donation after circulatory death: current status. Curr Opin Anaesthesiol 2013;26:382-390.
    1. De Carlis L, De Carlis R, Lauterio A, Di Sandro S, Ferla F, Zanierato M. Sequential use of normothermic regional perfusion and hypothermic machine perfusion in donation after cardiac death liver transplantation with extended warm ischemia time. Transplantation 2016;100:e101-e102.
    1. Fondevila C, Hessheimer AJ, Ruiz A, Calatayud D, Ferrer J, Charco R, et al. Liver transplant using donors after unexpected cardiac death: novel preservation protocol and acceptance criteria. Am J Transplant 2007;7:1849-1855.
    1. Hessheimer AJ, Coll E, Torres F, Ruíz P, Gastaca M, Rivas JI, et al. Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation. J Hepatol 2019;70:658-665.
    1. Gilbo N, Catalano G, Salizzoni M, Romagnoli R. Liver graft preconditioning, preservation and reconditioning. Dig Liver Dis 2016;48:1265-1274.
    1. Liu Q, Nassar A, Farias K, Buccini L, Baldwin W, Mangino M, et al. Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers. Liver Transpl 2014;20:987-999.
    1. Ghinolfi D, Lai Q, Dondossola D, De Carlis R, Zanierato M, Patrono D, et al. Machine perfusions in liver transplantation: the evidence-based position paper of the Italian Society of Organ and Tissue Transplantation. Liver Transpl 2020;26:1298-1315.
    1. Nanni Costa A, Grossi P, Gianelli Castiglione A, Grigioni WF; for Italian Transplant Research Network. Quality and safety in the Italian donor evaluation process. Transplantation 2008;85(suppl 8):S52-S56.
    1. Dondossola D, Lonati C, Zanella A, Maggioni M, Antonelli B, Reggiani P, et al. Preliminary experience with hypothermic oxygenated machine perfusion in an Italian Liver Transplant Center. Transplant Proc 2019;51:111-116.
    1. Lazzeri C, Bonizzoli M, Valente S, Cianchi G, Migliaccio ML, Gensini GF, Peris A. The role of extracorporeal membrane oxygenation in donation after circulatory death. Minerva Anestesiol 2014;80:1217-1227.
    1. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22:696-699.
    1. Ghinolfi D, Rreka E, De Tata V, Franzini M, Pezzati D, Fierabracci V, et al. Pilot, open, randomized, prospective trial for normothermic machine perfusion evaluation in liver transplantation from older donors. Liver Transpl 2019;25:436-449.
    1. Dondossola D, De Falco S, Kersik A, Maggioni M, Di Girolamo L, Biancolilli O, et al. Procurement and ex-situ perfusion of isolated slaughterhouse-derived livers as a model of donors after circulatory death. ALTEX 2019;37:243-254.
    1. Dondossola D, Santini A, Lonati C, Zanella A, Merighi R, Vivona L, et al. Human red blood cells as oxygen carriers to improve ex-situ liver perfusion in a rat model. J Clin Med 2019;8:1918.
    1. Brockmann J, Reddy S, Coussios C, Pigott D, Guirriero D, Hughes D, et al. Normothermic perfusion: a new paradigm for organ preservation. Ann Surg 2009;250:1-6.
    1. Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010;16:943-949.
    1. Aggarwal S, Kang Y, Freeman JA, Fortunato FL, Pinsky MR. Postreperfusion syndrome: cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplant Proc 1987;19(suppl 3):54-55.
    1. Thomas ME, Blaine C, Dawnay A, Devonald MAJ, Ftouh S, Laing C, et al. The definition of acute kidney injury and its use in practice. Kidney Int 2015;87:62-73.
    1. 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;96:508-513.
    1. De Carlis R, Di Sandro S, Lauterio A, Botta F, Ferla F, Andorno E, et al. Liver grafts from donors after cardiac death on regional perfusion with extended warm ischemia compared with donors after brain death. Liver Transpl 2018;24:1523-1535.
    1. Centro Nazionale Trapianti. CNT official data report. . Accessed April 30, 2019.
    1. Giannini A, Abelli M, Azzoni G, Biancofiore G, Citterio F, Geraci P, et al.; for Working Group on DCD of Italian Society of Anesthesiology, Analgesia and Intensive Care (SIAARTI); Italian Society for Organ Transplantation. “Why can’t I give you my organs after my heart has stopped beating?” An overview of the main clinical, organisational, ethical and legal issues concerning organ donation after circulatory death in Italy. Minerva Anestesiol 2016;82:359-368.
    1. Larsen AI, Hjørnevik AS, Ellingsen CL, Nilsen DWT. Cardiac arrest with continuous mechanical chest compression during percutaneous coronary intervention. A report on the use of the LUCAS device. Resuscitation 2007;75:454-459.
    1. Eichhorn S, Mendoza A, Prinzing A,Stroh A, Xinghai L, Polski M, et al. Corpuls CPR generates higher mean arterial pressure than LUCAS II in a pig model of cardiac arrest. Biomed Res Int 2017;2017:5470406.
    1. Gates S, Quinn T, Deakin CD, Blair L, Couper K, Perkins GD. Mechanical chest compression for out of hospital cardiac arrest: systematic review and meta-analysis. Resuscitation 2015;94:91-97.
    1. Net M, Valero R, Almenara R, Barros P, Capdevila L, López-Boado MA, et al. The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation. Am J Transplant 2005;5:2385-2392.
    1. Schlegel A, Scalera I, Perera MTPR, Kalisvaart M, Mergental H, Mirza DF, et al. Impact of donor age in donation after circulatory death liver transplantation: is the cutoff “60” still of relevance? Liver Transpl 2018;24:352-362.
    1. Watson CJE, Jochmans I. From, “gut feeling” to objectivity: machine preservation of the liver as a tool to assess organ viability. Curr Transplant Rep 2018;5:72-81.
    1. Xia W, Ke Q, Wang Y, Feng X, Guo H, Wang W, et al. Donation after cardiac death liver transplantation: graft quality evaluation based on pretransplant liver biopsy. Liver Transpl 2015;21:838-846.
    1. Flechtenmacher C, Schirmacher P, Schemmer P. Donor liver histology-a valuable tool in graft selection. Langenbecks Arch Surg 2015;400:551-557.
    1. Nasralla D, Coussios CC, Mergental H, Akhtar MZ, Butler AJ, Ceresa CD, et al.; for Consortium for Organ Preservation in Europe. A randomized trial of normothermic preservation in liver transplantation. Nature 2018;557:50-56.
    1. Dutkowski P, Schlegel A, De Oliveira M, Müllhaupt B, Neff F, Clavien PA. HOPE for human liver grafts obtained from donors after cardiac death. J Hepatol 2014;60:765-772.
    1. Bejaoui M, Pantazi E, Folch-Puy E, Baptista PM, García-Gil A, Adam R, Roselló-Catafau J. Emerging concepts in liver graft preservation. World J Gastroenterol 2015;21:396-407.
    1. Hessheimer AJ, Fondevila C. Liver perfusion devices: how close are we to widespread application? Curr Opin Organ Transplant 2017;22:105-111.
    1. Muller X, Schlegel A, Kron P, Eshmuminov D, Würdinger M, Meierhofer D, et al. Novel real-time prediction of liver graft function during hypothermic oxygenated machine perfusion before liver transplantation. Ann Surg 2019;270:783-790.
    1. Mergental H, Perera MTPR, Laing RW, Muiesan P, Isaac JR, Smith A, et al. Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transplant 2016;16:3235-3245.
    1. Matton APM, de Vries Y, Burlage LC, van Rijn R, Fujiyoshi M, de Meijer VE, et al. Biliary bicarbonate, pH, and glucose are suitable biomarkers of biliary viability during ex situ normothermic machine perfusion of human donor livers. Transplantation 2019;103:1405-1413.
    1. Dar WA, Sullivan E, Bynon JS, Eltzschig H, Ju C. Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms. Liver Int 2019;39:788-801.
    1. Gao X, Zhang H, Belmadani S, Wu J, Xu X, Elford H, et al. Role of TNF-alpha-induced reactive oxygen species in endothelial dysfunction during reperfusion injury. Am J Physiol Heart Circ Physiol 2008;295:H2242-H2249.
    1. Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 2015;6:524-551.
    1. Chae MS, Kim Y, Chung HS, Park CS, Lee J, Choi JH, Hong SH. Predictive role of serum cytokine profiles in acute kidney injury after living donor liver transplantation. Mediators Inflamm 2018;2018:8256193.
    1. Ellett JD, Atkinson C, Evans ZP, Amani Z, Balish E, Schmidt MG, et al. Murine Kupffer cells are protective in total hepatic ischemia/reperfusion injury with bowel congestion through IL-10. J Immunol 2010;184:5849-5858.

Source: PubMed

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