4th advanced interactive transplant course hammersmith … · 2010. 11. 1. · david paredes zapata...

4th Advanced Interactive Transplant Course 4th Advanced Interactive Transplant Course Hammersmith HospitalHammersmith Hospital

October 11October 11--13, 201013, 2010

SOCIETYSOCIETY

DONATIONDONATION

EXTRACTIONEXTRACTION

TRANSPLANTATIONTRANSPLANTATION

FollowFollow--upup Social AttitudeSocial Attitude

ProcurementProcurementSharingSharing

THE NEW VITAL CYCLE

David Paredes Zapata

Transplant Services Foundation

Associate Profesor

Surgery Department

Medical School

University of Barcelona

H CLÍNIC DE BARCELONA

dparedes@clinic.ub.es

USE OF KIDNEYS FROM MAASTRICHT USE OF KIDNEYS FROM MAASTRICHT CATEGORY 1 AND 2 NONCATEGORY 1 AND 2 NON--HEART BEATING HEART BEATING

DONORS: DONORS:

YES WE CAN!YES WE CAN!

Classification of MaastrichtCategory Condition Event Frequency

1 Uncontrolled Death on arrival Rare

2 Uncontrolled CPR maneuversunsuccessful

Very frequent

3 Controlled Removal of ventilatorysupport followed by

cardiac arrest

LessFrequent

4 Uncontrolled Brain death followed bycardiac arrest

Rare

CPR, cardiopulmonary resuscitation

NHBD

CARDIAC ARREST

TRANSPORT

(II)

PATIENT in P-CPR

(I)

DIAGNOSIS ofDEATH

ORGAN PERFUSION

HARVESTING

OUTSIDE HOSPITAL OUTSIDE (INSIDE) HOSPITAL

HO

SPIT

AL

AWAITINGCARDIAC ARREST (III)

WITHDRAWAL OF SUPPORT

CARDIAC ARREST in a DBD (IV)

Donors after Cardiac Death. Maastricht Categories.

DEAD ON ARRIVAL

- Law 30/1979 de 27 de October- R.D. 426/1980 de 26 de February- 1995 First International Workshop on NHBD. Maastricht- 1995 National Consensus Document (ONT)- R.D. 2070/1999 de 30 de December

“…it can be considered acceptable to start measures guided to preserve the organs with the possibility of a posterior transplant, while detecting relatives who can transmit the donation will of the death person…”

“ The procurement of organs from NHBD Type III of Maastricht is excluded from the consensus document until further regulations due to ethical reasons.”

- Criteria for the diagnosis of cardiac death.- Procedure after the diagnosis of cardiac death.

REGULATION REGULATION -- LEGISLATIONLEGISLATION

Cardiac arrestCardiac arrest

20 min20 min

30-40 min30-40 min

60-90 min60-90 min

NR Graftretrieval

Control: No CA; No NRControl: No CA; No NR

Monitoring

Monitoring

30-60… min30-60… min

Liver Transplant

4/6/8/12 hoursCold Ischemia Time

Donors after Cardiac Death. Experimental Model with Clinical Applications

Cold StoragePerfusion Machines

Is PTBC

- 1986 Started Protocol at H. Clínic- Others protocols started (H. Bellvitge)- 1995 National Consensus Document ONT /

First International Workshop on NHBD, Maastricht- 1998 SCUB, S.A. 061 – H. Clínic Protocol- 2002 SEM – H. Clínic Protocol- 2005 OCATT Comission for developing NHBD program in

Catalonia- 2006 Start of Catalonia NHBD Protocol (1st February – 1st May)

Donors after Cardiac Death. Historical background in Catalonia

I. Extrahospitalary CRA that, after a period of >30 minutes of advanced CPR maneuvers, it’s irreversible, and the ALS is maintained for transporting to the specific reference center (with independence of the geographic place) only with the aim of obtaining the organ and tissue donation.

II. CRA inside or outside the hospital. The transport to the hospital is done with a therapeutic aim and after advanced CPR maneuvers, reanimation is not achieved and the patient is declared death.

III. Awaiting cardiac arrest.

IV. Cardiac arrest while brain death

ACTIVATION OF CODE 3.03

CATASISTOL PROTOCOLCATASISTOL PROTOCOLBarcelona ClassificationBarcelona Classification

1986 1986 -- 1998 / 1998 1998 / 1998 -- 2002 / 2002 2002 / 2002 –– 20062006------ / SCUBSA/ SCUBSA--061 / SEM061 / SEM

2006 2006 -- 20072007

2007 2007 -- 20102010

TRANSPLANTCOORDINATION UNIT

OUT OF HOSPITALEMERGENCY

SERVICES(SEM)

OCATT / ONT

LIVERSURGERY

UROLOGY / RTU

Pathology ERLabImmunologyInfectious

Dept.Microbiology

ER & SURGERYNURSES

EMER

GEN

CY

AR

EA

TRANSPLANT HOSPITALS

EMERGENCY

MULTIDISCIPLINARY PROGRAMMULTIDISCIPLINARY PROGRAM

DCD Procedures

TRANSPLANT2 ½ hours30 min.

RECOVERY

PRESERVATION

CPR

CARDIACARREST

DXDEATH

PERFUSION

DONORS AFTER CARDIAC DEATH TYPE IIDONORS AFTER CARDIAC DEATH TYPE II

5 MINUTES

TRANSPLANT30 min.

RECOVERY

PERFUSIONASYSTOLIA DXDEATH

DCD Procedures

WITHDRAWALTREATMENT

DONORS AFTER CARDIAC DEATH TYPE IIIDONORS AFTER CARDIAC DEATH TYPE III

DCD PROTOCOLSDCD PROTOCOLS

TRANSPORT TO INTRAHOSPITALLARY CPR AREA

RECOVERING FROM CANO YES

STABILIZATION AND TRANSPORT TO HOSPITALSEM EVALUATIONCRITERIA ACTIVATION

DCD PROTOCOL (CODE 3.03)

Donors after Cardiac Death. CA – CPR – Code 3.03

CARDIAC ARREST (CA)

ACTIVATION CODE 3.03: Tx Coordinator (2) – Emergency Area – OCATT

SEM ACTIVATION

STARTING ADVANCED CPR MANOEUVRES

ARRIVAL TO INTRAHOSPITALLARY CPR AREA

DIAGNOSIS and CERTIFICATION OF DEATHNO YES

CODE 3.03DESACTIVATION

THE DEAD PATIENTBECOMES

A POTENCIAL DCD

Donors after Cardiac Death. Intrahospitalary Care and Dx of Death

MEDICAL ATTENDANCE TO THE PATIENT

DEATH DIAGNOSISDEATH DIAGNOSIS

• DEATH DIAGNOSIS(Internal Medicine/Anesthesiology)

• Judicial – No Judicial

• Activation – No activation DCD Procedure

• Non-touch Period (5 Minutes)

• Transfer Potential Donor Cannulation Box• Blood Sampling

– Serologies & microbiology– Biochemistry– Immunology– Judicial samples

• HEPARINIZATION (3 mg/kg)• IV Pantoprazol

YES NO

ACTIVATION OF THE DCD TEAM

EVALUATIONACTIVATION CRITERIA

DCD PROTOCOL(2 MEDICAL TRANSPLANT COORDINATORS + Medical

student)

DCD PROTOCOLDESACTIVATION

DCD PROTOCOL ACTIVATION

Donors after Cardiac Death. DCD Protocol Activation.

1 General surgeons1 Urologist1 Anesthesiologist1 OR Nurse1 ER Nurse

TRANSPORT TO THE DCD CANULATION AREA

– Age: 14 (40kg) to 65 years old

– Pure Warm Ischemic Time ≤ 30 minutes (CA – Start CPR)– Total Warm Ischemic Time < 150 minutes (CA – Start Organ Preservation)– Hemodynamic Instability previous to CA < 90 minutes (ABP < 60mmHg)

– Absence of criminality or non clarified violent death

– Absence of technical difficulties• Need of the out of Hospital emergency service• Inoperability of the reference Hospital• Impossibility to assure adequate ventilation or cardiac massage

maneuvers• Extrahospitalary CPR period > 90 minutes

– Absence of absolute contraindication for donation• History of Neoplasia (past or active) (Exceptions)• HIV positive or biological risk factors for HIV (even HCV, HBV)• Non treated or uncontrolled systemic Infection • Prion Infection

INCLUSION INCLUSION -- EXCLUSION CRITERIAEXCLUSION CRITERIA

ORGAN PERFUSIONMETHOD (NR)

FAMILYCONSENT

TRANSPORT TO O.R.

ORGAN RECOVERY AND COLD PRESERVATION

FINAL ORGAN VIABILITY

CONFIRMATION ANDOFFER TO OCATT

TRANSPLANT REJECTION

ORGAN DISTRIBUTION FOLLOWING OCATT CRITERIA

STARTING OF ORGAN PRESERVATION PROCEDURES

Donors after Cardiac Death. DCD Protocol Activation.

LEGAL CONSIDERATIONS

SURGICAL CANULATION

JUDICIALCONSENT

(If Necessary)

FAMILY APROACH

• PREPARE DONOR– Undress– Nasogastric catheter– Urethral catheter– Shaving

• Contact to the Court & Coroner (Telephone / Fax)

• Femoral Vessels Cannulation

• Connection NECMO circuit

• Withdrawal CCP+Ventilation

• Thorax X-Ray (Fogarty control) + donor evaluation

PRESERVATION PROCEDURESPRESERVATION PROCEDURES

• Immediate Cooling Stop metabolic functions

– In situ Perfusion• Gravidity• Perfusion pump

– Total Body Cooling (CP By-pass)

• Normothermic Reperfusion (CP By-pass)Recover cellular metabolic functions

PRESERVATION TECHNIQUES PRESERVATION TECHNIQUES

Doble balloonTriple lumen catheter

Venous dreinage

PERFUSION PROCEDURESPERFUSION PROCEDURES

Am J Transplant. 2007; 7: 1849-1855

NECMOORGAN

PRESERVATION

Donors after Cardiac Death. Normothermic Recirculation (NECMO)

• Normothermic Recirculation 1-4h (6h) with a pump maintenance > 1.2-1.7 L/m2

• Continuos gasometric and ionic control (30 min)

• Biochemical renal & hepatic control

• Hemogram crontrol

• Re-heparinization (1,5 mg/kg/90min)

Donors after Cardiac Death. Normothermic Recirculation (NECMO)

Donors after Cardiac Death. Normothermic Recirculation (NECMO)

Phase I:Cardiac arrest

Phase II: Advanced ventilatory support

Phase III:NECMO

Phase IV:Cold perfusion

Time <15 min <150 min <4 h Rapid

Donor <65 yrs

No absolute contraindication

No criminality or violent death

Negative viral serologies

No pathology or trauma affecting continuity of abdominal/ femoral vasculature

Initial AST, ALT <3×Creatinine

Final AST, ALT <4×Creatinine

Adequate irrigation of all abdominal organs

Appropriate liver and kidney aspect before and after perfusion

Method Witnessed

Attempts at resuscitation made and unsuccessful

Continuous CPR maneuvers until cardiocompressor

Cardiocompressor during cannulation

Pump flow >1.7 L/min, with Fogarty in supraceliac aorta

- pH maintained 7.0-7.4

NECMO until cold perfusion

NHBD SELECTION CRITERIA

(C Fondevila et al, Am J Transpl, Jul 2007)

TRANSFER TO THE O.R. & RECOVERYTRANSFER TO THE O.R. & RECOVERY

THE QUICKER THE BEST

PERFUSION THROUGH THEFEMORAL CANNULAS

ORGAN MACROSCOPIC EVALUATIONORGAN MACROSCOPIC EVALUATION

ORGAN MACROSCOPIC EVALUATIONORGAN MACROSCOPIC EVALUATION

Renal screening procedure•• Evaluate kidney function (Evaluate kidney function (CreatinineCreatinine, Urea, sediment, , Urea, sediment,

ProteinuriaProteinuria, , CreatinineCreatinine clearenceclearence))

•• Abdominal UltrasoundAbdominal Ultrasound

•• Macroscopic evaluation Macroscopic evaluation

•• > 60y + CVRF> 60y + CVRF•• Per operative Kidney BiopsyPer operative Kidney Biopsy•• RMP Hemodynamic evaluationRMP Hemodynamic evaluation Biopsy

+RPM

26 24

14

2423 2124

21 21

11

3137 35

47

65

73

43

2929

37

46

37

1723

17

3130

42

1231

11

84743433

0

10

20

30

40

50

60

70

2002 2003 2004 2005 2006 2007 2008 2009

BD (HC) BD (RH) NHBD Living Domino

NumberNumber and and typetype of of organorgan donorsdonors H. ClinicH. Clinic

97 111 93 126 99 111 115 137

KidneyKidney Transplant H Clinic Transplant H Clinic

119 11699

126 117

86 8976 78

16

818

16 22

5

1224

3029

41

60

109

6

61002

8

75

0

20

40

60

80

100

120

140

160

180

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

LivingNHBDBD

113 144 126 157 124 136121126 133 160

58

89

6675 71

79 72

41

1

42

73

4

7

13

9

4

76

56

2

6

3

4

33

67

2

2

69

2

24

0

20

40

60

80

100

120

2002 2003 2004 2005 2006 2007 2008 jul-05 Sep 10

DominoLivingNHBDBD

75 104 76 89 80 89 95 80

Liver Transplant H. Clinic56

5060

66,6

80

53,3

71,4

33,3

77,7 76,4

0102030405060708090

100

2002 2003 2004 2005 2006 2007 2008 2009 Sept.10

(%)2 5 9 12 10 15 17 14 10

DCD Liver Transplant H. Clinic

12 2

123

4

2

2

9

7

10

4

10

4

16

7

0

4

8

12

16

20

2002 2003 2004 2005 2006 2007 2008 2009 Sept.10

H. Clínic Espanya

DCD Liver Transplant H. Clinic - Spain

010203040506070

86 88 90 92 94 96 98 '00 '02 '04 '06 '08

ACTIVATIONS DONORS

IsP PIsP G

TBC NR

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

143 (43%)Real Organ Donors

210 (63%)Real Tissue Donors

20 (6%)Judicial Refusals

38 (11%)Family Refusals

132 (39%)Clinical Contraindications (%)

333Potential Donors

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

Age 47,3 ± 13,5 (65 – 17)

Sex ♀ 1: 5 ♂

Cause of Death

- Cardiovascular

- Brain Trauma

- Politraumatism

- Anoxia

- CVA

Clinical Contraindications

- Inadequate Perfusion

- Prolonged warm ischemia

- Deficient venous return

- Neoplasies

- Positive serologies

- Biological risk factors

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

0

50

100

150

200

250

CRA CPR Cardiocompressor Canulation NR

Min

.

8 ± 5,1

54,2 ± 16,2

34,1 ± 8,6 26,6 ± 14,1

183,1 ± 50,2

8,1 45 36 23 180MedianAverage

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

7

654

43

3622

‘98

4

442

32

3224

‘99

5

414

34105

2117

77

‘08

3

420

35148

2418

108

‘09

2

717

25104

2316

88

‘07

7

443

22

3225

‘00

211

45

23

23

122

Livers Tx

042

00

1814

‘01

7655

7151

7156

5645

4937

DCD SpainRealEffective

1

626

33

‘02

8

1378

127

‘06

6

1793

1814

‘05

74Lungs Tx

1180

671

Kidneys Tx

116

84

DCD CatalunyaRealEffective

‘04‘03

DCD vs. Total Number of Donors >6% (2009)

DCD 2,3 Donors p.m.p. (2009)

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

4

34

21

17

‘08

4

35

24

18

‘09

7

25

23

16

‘07

24221TransplantedLivers

6

3

3

‘02

13

12

7

‘06

17

18

14

‘05

116TransplantedKidneys

11

6

8

4

Real DCD

Effective DCD

‘04‘03

DCD vs. Total Number of Organ Donors >6% (2009)

DCD 2,3 Donors p.m.p. (2009)

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

DCPFRVD y/o mala perfusión en la

extracción

2 riñones MPR

R< 0,40 Bx: 0-3

R> 0,40 Bx: 0-3

R< 0,40 Bx: 4-6

R> 0,40 Bx: 4-6

TX No TX

TX Doble

Si DCP

No TX

Sin FRVD y buenaperfusión en la

extracción

Bx >= 7

No TX

1 Riñón MPR

R< 0,30

TX

1 Riñón

R> 0,30

No TX

TX

IF < 8 horas

Alguno de los siguientes factores

+ Biopsia renal

LEYENDA:DCP: Donante a corazón paradoME: muerte encefálicaRVD: Riesgo de viabilidad disminuidaR: Resistencia renal de perfusiónBx: Valoración histologica biopsia renalMPR: Máquina de perfusión renalTX: Trasplante IF: Isquemia fría

Criterios de Inclusión (Uno o más de los siguientes RVD):• > 60 años• HTA• DM• AVC sin lesión vascular cerebral conocida• Enfermedad arteriosclerótica y/o cardiopatia isquemica• Pacientes con daño cerebral severo con CID• Implante con Isquemia Fría > 15 horas, excepto riñones que en el momento de la conexión en máquina superen 6 horas de preservación estática

ALGORITMO MÁQUINA DE PERFUSIÓNConsensuado en reunión conjunta Trasplante Renal-Coordinación de Trasplantes en el 29 de Junio de 2005.

Dr. Campistol, Dr. F. Oppenheimer, Dr. R. Gutierrez, Dr. J. Vilardell, Dr. D.Paredes, Dr. R. Boni.

NS47,7 ± 12,7a50,1 ± 11,7aAge

0,0174.9%22,7%HBP

NSH: 85,7%M: 14,3%

H: 82,8%M: 17,2%

Gender

0,0414,3%28,7%Age >60y

0,017IAM: 69,4%AVC: 6,1%

IAM: 69%AVC: 12,6%

Cause ofdeath

NS4,7%8%DM

pCS n:74PP n:87

DCD Kidneys in Hospital Clinic(January 1999 – December 2008)

n=161

Donors after Cardiac Death. Renal Pulsatile Perfusion Machine.

33 (20,5%)

128 (79,5%)90 H CLINIC38 OTHERS

161

TOTAL

7487

NS58 (78,3%)44 H CLINIC14 OTHERS

70 (80,4%)46 H CLINIC24 OTHERS

Transplanted

NS16 (21,7%)17 (19,6%)Rejected

pCSPP

0,0156,676,7Final Perfusion Flow (ml/min)

0,0651,250,83Initial RR0,030,650,22Final RR

pDiscarded(n=17)

Transplanted(n=70)

Perfused Kidneys (n=87)

RR<0.4, Flow >70 mL/min

Donors after Cardiac Death. Renal Pulsatile Perfusion Machine.

NS21,723,1CIT > 17h (%)

NS4,023,69Cr a 1 month (mg/dl)NS5,045,32Cr (mg/dl)

0,00595,272,5H. Stay > 10 días (%)

0,0517,363,05Nº HD sessions

NS1,711,67Cr al 1st year (mg/dl)

0,173/44 (6,8%)0/46 (0%)PNF (%)0,0235/44 (79,5%)28/46 (60, 9%)DGF (%)

0,05288%100%Survival at 1st year

0,00132,8120,35Hospitalary Stay (días)

NS12,5613,39Cold Ischemic Time (h)

pCS(n=44)

PP(n=46)

Transplanted Kidneys at H Clinic de Barcelona

Donors after Cardiac Death. Renal Pulsatile Perfusion Machine.

0

20

40

60

80

100

%

DCD 35,7 60,7 3,6

IF DGF PNF

Incidence of Delayed Graft Function

s Cr 541,71,71,82,04,3

DaysNadir12m6m3m1m

1m 3m 6m 12m Nadir Days0.00.51.01.52.02.53.03.54.04.55.05.5

0

25

50

75

NHBD

mg/

dL

days

Serum Creatinine

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

89,291,7

88,9

0

10

20

30

40

50

60

70

80

90

100

2004-2008

DCD DBD DCD + DBD

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

47 Liver donors

17 OLT (36%)Causes for no-transplant (30)Steatosis 9 (30%)Poor perfusion 6 (20%)Transaminase elevation 3 (10%)Peritonitis 3 (10%)Hepatic trauma 2 (6.7%)Age & long ischemia 2 (6.7%)Age & antecedents 2 (6.7%)Fibrosis 1 (3.3%)Alcoholic cirrhosis 1 (3.3%)Active tuberculosis 1 (3.3%)

OUTCOMES OF POTENTIAL DCD

04/02 – 12/07

2/3

Liver Transplantation Interdisciplinary Conference March 13 - 14, 2009, Barcelona

Liver Transaminases during NR

0

50

100

150

200

250

0 1 2 3 4

Time (h)

IU/L AST

ALTn=13

n=13n=13n=8 n=3

Donors after Cardiac Death. Transaminase Levels of Transplanted Livers.

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

OUTCOME OF UNEXPECTED NHBD

Median follow-up: 14.5 months (r= 0-77)

64%74%

4 cases censored for patient death n= 22

3,3 3,43,7

2,52,7

2,5 2,42,6

2,82,6

3,43,5

3,3 3,4

1,61,8

1,41,2

2,9

1,31,21

2,93

2,52,72,7 2,8

0

0,5

1

1,5

2

2,5

3

3,5

4

2003

2004

2005

2006

2007

2008

2009

2003

2004

2005

2006

2007

2008

2009

Generated Organs / Donor Transplanted Organs / Donor

BD DCD

RESULTS OF THE DCD PROGRAMRESULTS OF THE DCD PROGRAM

AGRADECIMIENTOS

UNIDAD DE DONACIÓN – EQUIPO PERFUSIÓN RENALAngel Ruiz, David Paredes, Camino Rodriguez, Anna Vilarrodona, Marta Alberola, EsteveTrias, Marti Manyalich y Blanca Miranda. Elba Agusti, Nausica Otero.

UROLOGÍALluis Peri, Eduard García-Cruz, Rafael Gutierrez del Pozo†, Antonio Alacaraz.

UNIDAD DE TRASPLANTE RENALFrederic Oppenheimer, Josep Maria Campistol, Vanesa de la Fuente

CIRUGÍA HEPÁTICAJuan Carlos Garcia Valdecasas, Josep Fuster, Constantino Fondevila, David Calatayud

SEMSAPilar Palma, Josep M. Soto, Antonio Carballo, Jacinto Gallardo, Quim Rios, Fernando Garcia

OCATTMargarita Sanroma, Alba Ribalta, Roser Deulofeu

IGLMarc Net, Silvina RamellaWATERS MEDICAL SYSTEMSChuck Patrick

DMC

– PERFUSION IMPROVEMENT

– DCD TYPE III

– ORGAN PERFUSION MACHINES

– COLABORATION WITH NEW CENTERS WITH DCD PROGRAMS

– DEVELOPMENT LUNG PROGRAMS

– DEVELOPMENT EXPERIMENTAL PROGRAMS

FUTURE STRATEGIESFUTURE STRATEGIES

BARCELONA NMP MODELBARCELONA NMP MODEL

USE OF KIDNEYS FROM MAASTRICHT CATEGORY 1 AND 2 NONUSE OF KIDNEYS FROM MAASTRICHT CATEGORY 1 AND 2 NON--HEART BEATING DONORS: HEART BEATING DONORS:

YES WE CAN!YES WE CAN!