Hypothermic or normothermic abdominal regional perfusion: strategies and selection criteria for NHBD (Systems ECMO)

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Hypothermic or normothermic abdominal regional perfusion: strategies and selection criteria for NHBD (Systems ECMO) Constantino Fondevila Associate Professor of Surgery HPB & Liver Transplant Surgery Hospital Clínic, University of Barcelona, Spain

ORGAN QUALITY Fewer and fewer ideal organs 1980 1990 2000 2010

Donor 20% Donor 300% The greatest potential lies with uncontrolled NHBD, but changes are needed from Governments to provide a clear legal framework, funding and training for the infrastructure and acceptance by the public. Deshpande R & Heaton N, J Hepathol 2006.

DCD Preservation Injury Minutes Hours

Intrahepatic liver abscesses after DCD Liver Transplant Lens S et al, Med Clin (Barc). 2012.

Technique Perfusion in situ Thoraco-abdominal compressions Hypothermic recirculation Normothermic recirculation Results Quick and easy. Inferior results (kidney). Simultaneous chest (mechanical) and abdominal (manual) compressions with the aim of maintaining MAP 70 mmhg and PaO2 100 mmhg. 1,2 Primarily used to maintain Maastricht type III donors. Variable results, with high rates of DGF in some series (kidney). Little experience in Maastricht type II donors. 1,2 Better immediate function, technique of choice for the preservation of abdominal organs. 3,4

normothermic (Curr Opin Organ Transplant 2016, in press)

normothermic (Curr Opin Organ Transplant 2016, in press)

Experimental model (swine)

AST IU/L 6000 5000 4000 3000 2000 1000 0 p<0.05: CA = 90 min* G1 vs. G2 12, 24 h 0 20 40 60 80 100 120 Time (h) (*Previous heparinization) 5 DAY SURVIVAL G1:0% G2:83% 4 h CS (G1) 1 h NECMO + 4 h CS (G2) C Fondevila. Ann Surg 2011

Reconditioning ISCHEMIA UNCONTROLLED DCD CONTROLLED DCD OHCA Resuscitation maneuvers Declaration of death Cannulation with continuous chest compressions & mechanical ventilation Life support withdrawal Progressive hypotension & desaturation CARDIAC ARREST Declaration of death Normothermic Regional Perfusion Normothermic Regional Perfusion Organ & donor evaluation Organ evaluation Organ recovery Organ recovery

udcd CARDIAC ARREST TRANSPORT HOSPITAL AARIVAL DEATH DECLARATION CANNULATION NRP (Modified from: Fondevila C y cols, Am J Transpl 2007. doi: 10.1111/j.1600-6143.2007.01846.x)

CPR & death diagnosis Organ preservation

Hospital Clínic Barcelona 1,2 Normothermic regional perfusion Tº 37 ºC ph 7.35-7.45 PaO 2 Hct >20% Initial AST, ALT Final AST, ALT Pump flow Heparinization Time 100-150 mmhg <3 x ULN <4 x ULN >1.7 L/min with Fogarty in supraceliac aorta 1.5 mg/kg every 90 min. <4 hours Fondevila C, Am J Transplant 2007. Fondevila C, Dig Liver Dis Suppl 2009.

Fondevila et al, Am J Transplant 2012.

NRP 16:50 Laparotomy 17:35

NRP 16:50 Laparotomy 17:35 DO 2 = Flow x [(SO 2 x 1.34 x Hb) + (0.0031 x PO 2 )]

IC ReTx 1-y Graft Survival 1-y Patient Survival Barcelona, 2012 34 udcd 538 DBD 3 (9%) 3 (9%) 70 vs 87% (p=0.01) 82 vs 90% (p=0.14) Paris/Clichy/ Villejuif, 2014 13 udcd 41 DBD 1(7.6%) 3 (23%) 69 vs 93% (p=0.03) 85 vs 93% (p=0.39)

N Source 1-yr graft survival 1-yr patient survival IC All biliary complications Abt 2003 15 UPenn 72% 79% 27% 33% Chan 2008 52 UWash ~80% ~84% 14% -- de Vera 2007 141 Pitt 69% 79% 16% 25% Dezza 2007 13 Ghent 54% 62% 23% -- Foley 2011 87 Wisconsin 69% 84% 34% 47% Fujita 2007 24 Florida 69% 87% 13% -- Grewal 2009 108 Mayo (FL) 79% 92% 8%* -- Kaczmarek 2007 11 Newcastle 73% 82% 27% 45% Maheshwari 2007 20 Hopkins 55% 75% 50% 60% Manzarbeitia 2004 19 Albert Einstein -- 90% -- 11% Pine 2009 39 St. James (UK) 80% 80% 21% 33% Skaro 2009 32 Northwestern 61% 74% 38% 53% DeOliveira 2011 167 King s College 90% 90% 2.5% 15% *Only cases leading to graft loss. Fondevila 2011 34 Barcelona 70% 82% 9% 12% Uncontrolled

Stringent criteria Davila D. Am J Transplant 2012.

udcd CARDIAC ARREST TRANSPORT HOSPITAL AARIVAL DEATH DECLARATION CANNULATION NRP cdcd* CANNULATION LIFE SUPPORT WITHDRAWAL CARDIAC ARREST DEATH DECLARATION CANNULACION NRP *Spanish Royal Decree 1723/2012 (Modified from: Fondevila C et al, Am J Transpl 2007. doi: 10.1111/j.1600-6143.2007.01846.x)

Novel Technologies for Organ Transplantation Working Group To identify and evaluate new techniques and technologies for the preservation/reconditioning of retrieved organs with a view to increase organ utilisation. In-situ normothermic perfusion in category II DCD donation and applicability to DCD III. Taking Organ Transplantation to 2020: A UK strategy. June 2013. Available at: www.nhsbt.nhs.uk/to2020

- 8 controlled DCDs - Organs transplanted: 3 livers 2 pancreas 14 kidneys In summary, this paper describes our early experience with normothermic regional perfusion. It enabled assessment of donor livers and has the potential to improve the early outcomes of other organs retrieved from controlled DCD donors without the need for prior heparinization or cannulation.

Oniscu GC et al, Am J Transplantation 2014.

Controlled DCD started in December 2014 Initial french experience (3 Hospitals, 5 donors, 3 livers transplanted) NRP mandatory (after CA, pre-catheterisation femoral vessels) (Data courtesy of Corinne Antoine)

15:42 15:40 15:42 15:44 15:50 CANNULATION Start 15:40 End 15:50