DCD Heart Transplantation Papworth Perspective Simon Messer Stephen Large
Objectives Heart transplantation in the UK DCD donation in the UK DCD impact on heart function Normothermic Regional Perfusion (NRP) Direct Procurement and Perfusion (DPP) NRP then cold storage (NRP/CS) How do they compare?
UK Heart Transplant Activity Figure 7.1 Deceased donor heart programme in the UK, 1 April 2004-31 March 2014, Number of donors, transplants and patients on the active transplant list at 31 March 250 246 Donors 200 Transplants Transplant list 200 204 198 Number 150 166 154 140 141 157 156 127 128 132 130 131 115 120 126 130 126 169 136 138 144 145 100 106 110 88 95 93 50 0 2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013 2013-2014 Year NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
UK Outcomes Following Listing Figure 7.3 Post-registration outcome for 87 new non-urgent heart only registrations made in the UK, 1 April 2010-31 March 2011 100 90 5 13 6 18 10 13 80 70 26 30 Percentage 60 50 40 52 37 18 11 30 20 31 39 45 46 10 0 6 months 1 year 2 years 3 years Tim e since listing Transplanted Still w aiting Removed NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf Died
The Rise of DCD Donation in UK
UK DCD Transplant Success Donation 1.1 to 18.3 (pmp) 1.9 to 11.7 (pmp) 0.2 to 2.2 (pmp) 0.5 (pmp)
Messer S, Lannon J, R Axell, Wong E, Hopkinson C, Fielding S, Ali A, Tsui S, Large S
Prior to withdrawal
Start of Functional Warm Ischaemia
Mechanical Asystole
ATP/ADP ratio ATP/ADP Ratio Following Withdrawal and Reperfusion 10 8 6 p=0.75 NRP DPP p=0.57 p=0.47 p=0.88 p=0.06 4 p=0.75 2 0 Nomoxia Anoxia 15 mins 60 mins 90 mins 150 mins Time (mins)
Techniques of DCD heart retrieval in UK Direct Procurement and Perfusion: normothermic machine perfusion during transportation Normothermic Regional Perfusion (NRP) followed by normothermic machine perfusion during transportation Normothermic Regional Perfusion (NRP) followed by cold static storage during transportation
Direct Procurement and Perfusion
Direct Procurement and Perfusion Advantages Simple to perform No additional blood products No additional staff No additional equipment Easy to teach to others Can work with any abdominal retrieval team
Direct Procurement and Perfusion Drawbacks Unable to functionally assess the heart Waste 45 000$ for every heart declined on rig Completely reliant on Lactate Short ischaemic times Donor age restricted to 50 years old Surgeons uncomfortable when extending the ischaemic time
Rising Lactate on the OCS
Normothermic Regional Perfusion Death declared Median Sternotomy Clamp Arch Vessels NRP Full Flow/Carotid Doppler Intubate and Ventilate
60 mins wean from NRP Swann Ganz / TOE Cardioplegia Instrument on OCS Transplant
Normothermic Regional Perfusion
Normothermic Regional Perfusion Advantages Allows a full functional assessment of the heart Shorter ischaemic time by 14 minutes Allows the surgeon to disregard lactate Allows the donor age to be extended Allows the ischaemic time to be extended Avoids the cost of placing a heart on the OCS that is turned down. Allows liver, kidneys, lungs and pancreas to be perfused Removes the haste from retrieval and organ damage
Normothermic Regional Perfusion Drawbacks Additional cost of 4500$ per run for equipment Ethical concerns of perfusing a cadaver Additional blood products- 6 units of packed red cells Additional 2 hours in donor hospital Additional personnel and equipment Retaining skills and training Working in collaboration with abdominal retrieval team
NRP and cold storage
NRP and Cold Storage Advantages Functional assessment of donor heart No cost of TransMedics OCS Donor age can be extended Warm ischaemic time can be extended
NRP and Cold Storage Drawbacks Reliant on donor and recipient co location Ethical concerns of perfusing organs within the cadaver Additional donor theatre time Additional personnel Additional equipment How long can the heart be cold stored for?
Extending the Boundaries Donor: 36 year old male ICH Withdrawal to death 139 minutes Withdrawal to blood perfusion 149 minutes After NRP CI 4.5L/min/m 2, CO 8.8L/min, HR 100bpm, CVP 7mmHg PCWP 6mmHg, MAP 104mmHg, EF 67%
Extending the Boundaries
Extending the Boundaries Recipient: 51 year old male HVAD OCS 428 min Off CPB on 3.8mcg/kg/min Dopamine, 0.05mcg/kg/min Adrenaline CI 2.5L/min/m 2, MAP 64mmHg, CVP 11mmHg 1 day mechanical ventilation 5 days ITU
Outcomes following Heart Transplantation from Donation After Circulatory Determined Death (DCD) Donors
Aim Are the early outcomes of DCD heart transplantation comparable to DBD heart transplants? What is the best method to procure the DCD heart? Normothermic Regional Perfusion (NRP) Direct Procurement and Perfusion (DPP) How much can DCD donors increase overall heart transplant activity by?
Method Single centre observational matched control study Comparing Consecutive DCD heart transplant patients between 01/02/15 to 31/07/16 Primary Outcome: 90 day survival Secondary Outcomes: Mechanical Support, Inotropic Support, Cardiac Performance, ITU duration, Mechanical Ventilation Duration, CVVH requirement, Hospital duration, Rejection Episodes
Method Matching: Donor: Age, sex and height Recipient: Age, sex and height, TPG, PVR, etiology, pre tx mechanical support Two retrieval techniques Normothermic Regional Perfusion (NRP) Direct Procurement and Perfusion (DPP)
Results
Donor Demographics DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 Age Yrs (MedIQR)) 37 (33-39) 34 (30-36) ns 37 (33-39) 34 (30-36) ns Male n (%) 18 (86) 14 (67) ns 9 (75%) 9 (100%) ns Height cm 175 (172-181) 178 (168-183) ns 175(169-180) 175(172-181 ns Cause of Death HBI n(%) 9 (42) 4 (19) 0.04 2 (17) 7 (78) 0.01 ICH n (%) 6 (29) 9 (43) 6 (50) 0 (0) TBI n (%) 5 (24) 2 (10) 3 (25) 2 (22) Other n (%) 1 (5) 6 (29) 1 (8) 0 (0)
Recipient Demographics DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 Age years Med(IQR) 58 (49-61) 59 (60-61) ns 59 (54-62) 50 (42-60) ns Male n (%) 18 (86) 18 (86) ns 10 (83) 8 (89) ns Height (cm) 174 (171-178) 173 (167-179) ns 174(169-175) 176(172-181) ns TPG (mmhg) 7 (5-8) 7 (4-8) ns 8 (7-8) 6 (4-6) ns PVR (Wood Units) 1.9 (1.4-2.2) 1.9 (1.5-2.4) ns 2.0 (1.7-2.2) 1.5 (1.3-2.1) ns
Recipient Demographics DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 Pre Tx VAD n (%) 4 (19) 4 (19) ns 1 (8) 3 (33) ns Aetilogy DCM (%) 12 (57) 12 (57) ns 9 (75) 3 (33) ns HCM n (%) 5 (23) 3 (14) 2 (17) 3 (33) RCM n (%) 0 (0) 2 (10) 0 (0) 0 (0) IHD n (%) 2 (10) 3 (14) 0 (0) 2 (22) VHD n (%) 1 (5) 1 (5) 1 (8) 0 (0) ARVC n (%) 1 (5) 0 (0) 0 (0 1 (11)
Ischaemic Timings NRP/DPP Time Median (IQR) NRP n=12 DPP n=9 P value Withdrawal to death (mins) 18 (13-21) 19 (15-23) ns Donation Withdrawal Ischaemic Time (mins) 24 (21-28) 38 (32-43) 0.005 Functional Warm Ischaemic Time (mins) 18 (15-20) 26 (23-31) 0.002 NRP Duration (mins) 41 (33-52) - - OCS Perfusion Time (mins) 170 (140-280 (206-0.02 179) 308) Implant Duration (mins) 32 (31-38) 36 (33-44) ns
Outcomes DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 Survival 30 day survival n (%) 21 (100) 21 (100) ns 12 (100) 9 (100) ns 90 Day survival n (%) 20 (95) 20 (95) ns 12 (100) 8 (89) ns Mechanical Support ns IABP n (%) 5 (24) 2 (10) ns 2 (17) 3 (33) ns ECMO n (%) 2 (10) 1 (5) ns 1 (8) 1 (11) ns VAD n (%) 1 (5) 0 (0) ns 0 (0) 1 (11) ns
Cardiac Performance ITU DCD vs. DBD NRP vs. DPP Inotropic Support DCD n=21 DBD n=21 NRP n=12 DPP n=9 Dopamine (mcg/kg/min) 4.2 4.5 0.05 4.7 3.2 ns Adrenaline (mcg/kg/min) 0.05 0.05 ns 0.04 0.05 ns Noradrenaline (mcg/kg/min) 0.00 0.04 ns 0.00 0.01 ns Cardiac Performance Cardiac Index (L/min/m 2 ) 2.5 (2.3-2.7) 1.9 (1.8-2.4) 0.01 2.5 (2.3-2.7) 2.5 (1.7-2.7) ns Cardiac Output (L/min) 4.7 (4.2-5.2) 3.8 (3.2-4.2) 0.002 4.9 (4.3-5.1) 4.6 (3.6-6.5) ns MAP mmhg 72 (64-81) 65 (58-69) 0.04 72 (64-81) 74 (66-79) ns CVP mmhg 9 (8-10) 10 (8-12) ns 10 (8-11) 9 (7-10) ns PAD mmhg 14 (12-17) 15 (12-18) ns 14 (13-16) 16 (13-18) ns
Outcomes DCD vs. DBD NRP vs. DPP DCD n=21 DBD n=21 NRP n=12 DPP n=9 Ventilation Duration (days) 0.6 (0.5-1.5) 2.1 (0.9-2.5) 0.05 0.6(0.4-1.1.1) 0.6(0.5-4.0) ns CVVH n (%) 5 (24) 6 (29) ns 3 (25) 2 (22) ns ITU Duration (days) 5 (3-5) 7 (6-9) 0.02 5 (4-5) 3 (3-7) ns Hospital Duration (days) 19 (17-26) 27 (19-34) ns 20 (18-27) 19(16-23) ns Rejection n (%) 9 (43) 13 (62) ns 4 (33) 5 (56) ns
Figure 5.3 Number of adult heart transplants in the UK, 1 April 2015 to 31 March 2016, by transplant centre 60 50 15 40 No. of transplants 30 20 10 22 36 4 21 26 29 0 Newcastle Papworth Harefield Birmingham Manchester Glasgow Transplant centre 7 DBD DCD Source: Annual Report on Cardiothoracic Transplantation 2015/16, NHS Blood and Transplant
Summary NRP reduces ischaemic time Allows donor age to be extended No longer reliant on Lactate Allows organ function to be optimised No difference in clinical outcomes in our series NRP/DPP