32nd spanish co-ordination congress - aforo...
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32nd Spanish Co-ordination Congress
Santander 19th October 2017
Stephen Large ma ms mrcp frcs(cth) frcs mba pae(rcp)
conflicts of interest 1. TransMedics: halved cost of disposables in one of our experiments 2. Novatis: advisor for annual transplant conference
Aims: 1. describe the reasons for and 2. development of DCD heart transplantation 3. results of DCD heart transplantation to date
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So what is the fuss all about? In
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AdultHeartTransplantsKaplan-MeierSurvivalbyEra
2016 JHLT. 2016 Oct; 35(10): 1149-1205
Median survival (years): 1982-1991=8.5; 1992-2001=10.4; 2002-2008=11.9; 2009-6/2014=NA
All pair-wise comparisons were significant at p < 0.05.
(Transplants:January1982–June2014)
SurvivalwithbestmedicalRx
AdultHeartTransplantsKaplan-MeierSurvivalbyEra
2016 JHLT. 2016 Oct; 35(10): 1149-1205
Median survival (years): 1982-1991=8.5; 1992-2001=10.4; 2002-2008=11.9; 2009-6/2014=NA
All pair-wise comparisons were significant at p < 0.05.
(Transplants:January1982–June2014)
Prognos;cValueadded
1Year(N=11,431) 3Years(N=9,766) 5Years(N=8,242)0%
20%
40%
60%
80%
100%10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2016 JHLT. 2016 Oct; 35(10): 1149-1205
AdultHeartTransplantsFunc;onalStatusofSurvivingRecipientsbyKarnofsky
Score (Follow-ups:January2009–June2015)
UK Heart Transplant Activity
166
154
140 141
157 156
127 128 132 130
115120
126131
136 138144 145
204198
2004-2005 2005-2006 2006-2007 2007-2008 2008-2009 2009-2010 2010-2011 2011-2012 2012-2013 2013-2014
Year
0
50
100
150
200
250
Num
ber
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
DonorsTransplantsTransplant list
106 110
8895 93
126 130
169
200
246
NHSBTAnnualReportonCardiothoracicTransplanta8on2013/2014.AvailableathBp//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
1. Tracking 147 patients on the routine list 1.4.12 for 3 years
Available at http//www.odt.nhs.uk/pdf organ_specific_report_cardiothoracic_2014.pdf
1. Tracking 147 patients on the routine list 1.4.12 for 3 years
2. Tracking patients on the urgent list for same period = 46% tx
Available at http//www.odt.nhs.uk/pdf organ_specific_report_cardiothoracic_2014.pdf
What to do? In
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AyyazA.AlietalEurJCardiothoracSurg(2007)31(5):929-933.
38/566 donors
DBD, living and DCD donation NHSBT 2016 report
0
200
400
600
800
1000
1200
1400
DBDdonors
Livingdonors
DCDdonors
07080910111213141516
NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
DBD, living and DCD donation NHSBT 2016 report
0
200
400
600
800
1000
1200
1400
DBDdonors
Livingdonors
DCDdonors
07080910111213141516
NHSBT Annual Report on Cardiothoracic Transplantation 2013/2014. Available at http//www.odt.nhs.uk/pdf/organ_specific_report_cardiothoracic_2014.pdf
Is DCD heart transplantation possible? Recent NHSBT update: probably 135 more donor /year
British Journal of Anaesthesia 108 (S1): i108–i121 (2012) Donation after circulatory death A. R. Manara 1*, P. G. Murphy 2 and G. O’Callaghan 3
3073DCDDonors
Consent 55DCDs(2%)NoYes
3018DCDs(98%)
Age<50years 2100DCDs(68%)
No
Yes
918DCDs(32%)
RiskFactors 563DCDs(17%)
Yes
382DCDs(12%)
Inotropes 330DCDs(11%)No
No
22DCDs(1%)
IncompleteData
171DCDs(6%)
YesYes
189DCDs(6%)
No
FWIT<30min
No22DCDs(1%)
149Poten;alDCDDonors(5%)
Yes
Is it needed? NHSBT (3 year period)
So can we use DCD donor hearts clinically?
• DCD results in profoundly ischaemic organs:
but how ischaemic?
PapworthHospitalNHSFounda;onTrust NHS
Method for modelling DCD (rat and pig)
AmJTransplant201111(8)1621-32AliAetal.
EnergystoresintheporcineDCDmodel
Ayyaz Ali PhD
Contractile reserve in isolated cardio-myocytes after isoproterenol administration: BSD vs. 15 min NHBD heart Am J Transplant 2011 11(8) 1621-32 Ali A et al.
Hearts from DCD donors display acceptable biventricular function after heart transplatation. Am J Transplant 2011 11(8) 1621-32 Ali A et al.
DCD heart transplantation: How tolerant the heart to normothermic ischaemia?
1. Ayyaz Ali PhD
2. Int Rev Cell Mol Biol. 2012 ; 298: 229–317. - and so for all organs
Ganote et al AJP 80(3) 1975 426
Tolerance to duration of ischaemia (canine):
DCD heart Tx BSD heart Tx
Left ventricle
Right ventricle
Orthotopic porcine heart transplant model
Hearts from DCD donors display acceptable biventricular function after heart transplantation. Am J Transplant 2011 11(8) 1621-32 Ali A et al.
Ayyaz Ali PhD
DCD v DBD donation:
Problem: DCD DBD Heart beating: X ✔✔
Brain damage ✔ ✔✔
Catecholamine storm ✔✔ ✔
So what about clinically ? In
!
Left and right ventricular pressure-volume loops from normal human heart.
Left and right P/V loops after resuscitation following 23 min normothermic arrest in the human
JHeartLungTransplant.2009Mar;28(3):290-3.AliAetal,
The Code Of Practice For The Diagnosis & Confirmation Of Death
• After 5 minutes of continued cardiorespiratory arrest, the absence of pupillary responses to light, of corneal reflexes, and of motor response to supra-orbital pressure is confirmed
• Diagnosing death in this situation requires
confirmation that there has been irreversible damage to the vital centres in the brain-stem due to the length of time in which the circulation to the brain has been absent.
• Cerebral perfusion should not be restored after
death has been confirmed
PapworthHospitalNHSFounda;onTrust NHS
www.odt.nhs.uk/pdf/code-of-prac8ce-for-the-diagnosis-and-confirma8on-of-death.pdf
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
MethodoforganprotecXon
followinginsults
Establishing blood supply for this ischaemic heart:
1. DPP direct procurement to perfusion Langandorff blood perfusion
2. NRP Normo-thermic reperfusion neck vessels ligated to prevent brain perfusion - limited perfusion with ECMO
1. Direct procurement and perfusion - DPP: 1
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
MethodoforganprotecXon
followinginsults
Establishing blood supply for this ischaemic heart:
1. DPP direct procurement to perfusion Langandorff blood perfusion
2. NRP Normo-thermic reperfusion neck vessels ligated to prevent brain perfusion - limited perfusion with ECMO
Thoraco-abdominal normothermic reperfusion TA-NRP:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
MethodoforganprotecXon
followinginsults
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
MethodoforganprotecXon
followinginsults
TransportaXonoforgantorecipienthospital
Timings following identification of futile treatment & consent for DCD organ donation:
Withdrawaloflifesupport(WLST)
FuncXonalwarm
ischaemia(FWIT)
Lossofpulse=asystole
+5minsconfirmaXonofDCDdeath
MethodoforganprotecXon
followinginsults
TransportaXonoforgantorecipienthospital
TransplantaXon
Method for modelling DCD (rat and pig)
WLST
FWIT
ASYSTOLE
REPERFUSION
DEATH
ANOXIA
SerumlactatelevelsinthebloodbasedperfusateoftheDCDdonorheartondonorNRPandOCSorECMS(extracorporealmachineperfusion)(MesserS2016bykindpermission)
ECMPTA-NRP
Timings DPP (15) NRP (13)
withdraw – asystole 33±53 25±39
asystole – blood perf. 21.6±2.2 13.2±2.4 (ischaemia) Death to Reperfusion 16 8
Functional Assessment Donor
Technique NRP 13 (DPP 15)
(Cardiac Index (L/min/m2) 3.4
CO (L/min) 6.7
Heart Rate (bpm) 114
CVP (mmHg) 5
PCWP (mmHg) 9
MAP (mmHg) 78
Ejection Fraction 65
Transplant DPP 15 NRP 13
OCS time 275±76 197±89
implant 37.4±10.7 35.2±5.9
Outcomes DCDvs.DBD NRPvs.DPP
DCDn=21 DBDn=21 NRPn=12 DPPn=9
VenXlaXonDuraXon(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
CVVHn(%) 5(24) 6(29) ns 3(25) 2(22) ns
ITUDuraXon(days) 5(3-5) 7(6-9) 0.02 5(4-5) 3(3-7) ns
HospitalDuraXon(days) 19(17-26) 27(19-34) ns 20(18-27) 19(16-23) ns
RejecXonn(%) 9(43) 13(62) ns 4(33) 5(56) ns
Outcomes DCDvs.DBD NRPvs.DPP
DCDn=21 DBDn=21 NRPn=12 DPPn=9
VenXlaXonDuraXon(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
CVVHn(%) 5(24) 6(29) ns 3(25) 2(22) ns
ITUDuraXon(days) 5(3-5) 7(6-9) 0.02 5(4-5) 3(3-7) ns
HospitalDuraXon(days) 19(17-26) 27(19-34) ns 20(18-27) 19(16-23) ns
RejecXonn(%) 9(43) 13(62) ns 4(33) 5(56) ns
Results
Other solid organ usage with DCD heart Tx:
Results
Retrieval Technique – NRP vs DPP
0%
4%
8%
12%
16%
20%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Incide
nceofCau
se-Spe
cificDeaths
Years
CAV AcuteRejec;onMalignancy(non-Lymph/PTLD) Infec;on(non-CMV)GraeFailure Mul;pleOrganFailureRenalFailure
2016 JHLT. 2016 Oct; 35(10): 1149-1205
Adult Heart Transplants Cumulative Incidence of Leading Causes of Death
(Transplants: January 1994 – June 2014)
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion
!
Take home messages: 1. 33 of 39 arrested? 2. Big catecholamine tide with DCD 3. Tricky assessment on OCS/TransMedics rig 4. Short and mid term outcomes comparable to DBD 5. Increasing annual activity by 33% 6. Costly rig perfusion 7. Perhaps some increased use of other organs
!
1. Can we make this a National programme? 2. Can we make the DCD heart more tolerant of normo- thermic ischameia ?
3. What I/R damage there is around death: can this be reversed/prevented? 4. Can these be expanded to the abdominal organs?
!
Musing?
Heart transplantation & DCD provision
Papworth
Harefield
Manchester
1. Can we make this a National programme? 2. Can this extend to other centres? 3. Can we make the DCD heart more tolerant of normo- thermic ischameia ?
!
Musings:
1. Can we make this a National programme? 2. Can this extend to other centres? 3. Can we make the DCD heart more tolerant of normo- thermic ischameia ?
!
Musings:
Is this so very far off?
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