32nd spanish co-ordination congress - aforo...

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

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

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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)



FuncXonalwarm

ischaemia(FWIT)



FuncXonalwarm

ischaemia(FWIT)

Lossofpulse=asystole



FuncXonalwarm

ischaemia(FWIT)


+5minsconfirmaXonofDCDdeath



FuncXonalwarm

ischaemia(FWIT)



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


FuncXonalwarm

ischaemia(FWIT)




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:


FuncXonalwarm

ischaemia(FWIT)




followinginsults



FuncXonalwarm

ischaemia(FWIT)




followinginsults

TransportaXonoforgantorecipienthospital



FuncXonalwarm

ischaemia(FWIT)




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

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

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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

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1. Can we make this a National programme? 2. Can we make the DCD heart more tolerant of normothermic ischameia ?

3. What I/R damage there is around death: can this be reversed/prevented? 4. Can these be expanded to the abdominal organs?

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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 normothermic ischameia ?

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Musings:

Is this so very far off?

32nd spanish co-ordination congress - aforo...

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