Franco Valenza

Department of Pathophysiology and TransplantationFondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Ex-Vivo Lung Perfusion for lung transplant.

No conflict of interest

Ex-Vivo Lung Perfusion for lung transplant.

Donation process

Ex-Vivo Lung Perfusion

Evaluation, Reconditioning, Repair

Economic consideration

Ex-Vivo Lung Perfusion for lung transplant.

Recipient

Cause of deathHistory

FunctionalMicrobiology

DiagnosisFunctional status

Clinical, InstrumentalVisual inspection

Biopsy

Organ

Multi-organ donor

IdealExtended criteria

Unacceptable

Van Raemndonck, Proc Am Thor Soc (2009);6:28

Van Raemndonck, Proc Am Thor Soc (2009);6:28

Pierre, J Thor Cardiovasc Surg (2002);123:421

pz in lista d'attesa trapianti effettuati

num

ero

0

20

40

60

80

100

120

Waitlist Lung Tx

death

… to safely increase the number of organs

Recipient

Cause of deathHistory

FunctionalMicrobiology

DiagnosisFunctional status

Procedure

Clinical, InstrumentalVisual inspection

Biopsy

Organ

Multi-organ donor

Donor treatment

Porro, Transpl Proc (2012); 44:1830

123 89

103

20 27

9

Autonomic Brain Storm

Diagnosis of Brain Death

Procurement

12

9

OR

ICU

Autonomic Brain StormBrain Death diagnosisOperating Room

First

P/F

0

100

200

300

400

500

Second Third

* *

RM 2 way Anova; *P<0.05 vs Autonomic Brain Storm

Mascia, JAMA 2010; 304(23):2620

Vt (ml/kg)

2 3 4 5 6 7 8 9 10 11 12 13 14

Paz

ient

i (N

)

0

10

20

30

40

50

60

70

PEEP (cmH2O)

1 2 3 4 5 6 7 8 9 10 11 12 13

Paz

ient

i (N

)

0

10

20

30

40

50

60

70

Singbarlt, Am J Transpl (2011); 11:1517

Recipient

Cause of deathHistory

FunctionalMicrobiology

DiagnosisFunctional status

Procedure

Clinical, InstrumentalVisual inspection

Biopsy

Organ

Multi-organ donor

Donor treatment

"Successive transition from one paradigm to another via revolution is the usual developmental pattern of mature science."

The Structure of Scientific Revolutions (1962)

Recipient

Cause of deathHistory

FunctionalMicrobiology

DiagnosisFunctional status

Procedure

Clinical, InstrumentalVisual inspection

Biopsy

Organ

Multi-organ donor Ex-Vivo Lung Perfusion

Jirsch DW, Fisk RL, Couves CM. Ex vivo evaluation of stored lungs. Ann Thorac Surg 1970;10:163-168.

Fisk RL, Symes JF, Aldridge LL, Couves CM. The pathophysiology and experimental therapy of acid pneumonitis in ex vivo lungs. Chest 1970;57:364-370.

Ex-Vivo Lung Perfusion

Steen, Ann Thor Surg (2003);76:244

EX-VIVO LUNG PERFUSION (EVLP): UNA POSSIBILE STRATEGIA PER AUMENTARE IL

NUMERO DI POLMONI DISPONIBILI PER TRAPIANTO.

Steen, Ann Thor Surg (2003);76:244

EX-VIVO LUNG PERFUSION (EVLP): UNA POSSIBILE STRATEGIA PER AUMENTARE IL

NUMERO DI POLMONI DISPONIBILI PER TRAPIANTO.

Ingemansson, Ann Thor Surgl(2009);87:255

Cypel, NEJM (2011);364:1431

Valenza, Transpl Proc (2011) 43:993

Valenza, Transpl Proc (2012) 44:1826

PaO2/FiO2 158 mmHg

Lung “Evaluation”

Lung “Reconditioning”

PaO2/FiO2 180 mmHg

Brain storm

Observation Retrival

Time (hours)

Flui

d ba

lanc

e (m

L)

CVP

Brain storm

Observation Retrival

Time (hours)

Brain storm

Observation Retrival

Time (hours)

Extended criteria

EVLP

Lungs available for transplantation

Non guidelines recipients

Is EVLP challenging the dogma?

Baseline Ischemia

EVLPPreservation

Reperfusion

Ischemia Reperfusion

EVLP

Thrombi, mediators Ischemia reperfusion injury

Preservation

Treatments (genes, drugs)

Baseline

Cypel, J Heart Lung Transplant (2008);27:1319

Martins, Gene Therapy (2004);11:1786

Eaton, Annu Rev Physiol (2009);71:403

Valenza, Transpl Proc (2011);43:993

PAPm

(mm

Hg)

0

5

10

15

20

25

30

REC 0 REC 60 REC 240

0 1 2 3 4

**

*

ControlBeta-agonist

Valenza, J Heart Lung Transpl (2012); 31:524

Beta agonist reconditioning of donor lungs

Extended criteriaLUNG EDEMA

EVLP

Lungs available for transplantation

Lung “Reconditioning”UnacceptableAB-INGESTISSECRETIONS

Lung “Repair”

Extended criteriaLUNG EDEMA

EVLP

Lungs available for transplantation

Lung “Reconditioning”UnacceptableINHALATIONSECRETIONS

Lung “Repair”

Prospective observational investigation123 subjects, 15 ICU

Time

Brain death Cold storage

REPERFUSION

Lung transplantation

Valenza, Intensive Care Med exp (2014)

Valenza, Intensive Care Med exp (2014)

Time (min)

0 60 120 180 240 300 360 420 480 540 600

ICP

(mm

Hg)

0

20

40

60

80

100

120

140

160

180

Time (min)

0 60 120 180 240 300 360 420 480 540 600

CPP

(mm

Hg)

-150

-100

-50

0

50

100

TREATMENTINDUCTION

Time

Brain death Cold storage

REPERFUSION

Lung transplantation

AB-INGESTIS

Donor treatment

High vs. Low PEEP donor treatment

Time

Brain death Cold storage

REPERFUSION

Lung transplantation

AB-INGESTIS

Donor treatment EVLP

“repair”

Matthay, Chest (2010);134:965

Valenza, Organs Tissue & Cells (2012)

Economic considerations

Economic considerations

Timing of the transplantation

Van Raemdonk, Transpl Int. 2014 Mar 15. doi:10.1111/tri.12317

Recipient

Organ

Multi-organ donor

AnesthestistPerfusionist

SurgeonNurse

2 Students

2 SurgeonsAnesthestist

2 Nurses

Know howClinical- preclinical

EVLP team

Procurement team

Padova

Bergamo

Milano

Pavia

EVLP pre-conditioning of the lung?

pz in lista d'attesa trapianti effettuati

num

ero

0

20

40

60

80

100

120

Waitlist Lung Tx

death

… in conclusion

Recipient

Cause of deathHistory

FunctionalMicrobiology

DiagnosisFunctional status

Clinical, InstrumentalVisual inspection

Biopsy

Organ

Multi-organ donor

Ex-Vivo Lung Perfusion

Donor treatment

pz in lista d'attesa trapianti effettuati

num

ero

0

20

40

60

80

100

120

decessi

DonorEVLP

Waitlist Lung Tx

death

… in conclusion

U.O. Anestesia e RianimazioneU.O. Chirurgia Generale ad Orientamento Toracico

Infermieri Camera Opreatoria ZondaCentro di Ricerche Chirurgiche Precliniche

Direzione Scientifica , Generale

Fondazione Ca’ Granda

Sponsors of the projectRegione Lombardia

Centro Nazionale TrapiantiLega Lombarda Fibrosi Cistica

Uknowledgments

Silvia, Sara, Jacopo, Alessandro, Giulia, Grazia, Stefano, Katia, Patrizia, Andrea, Daniele…

Research Team

… to you for your attention!

Uknowledgments

Department of Pathophysiology and Transplantation, Univeristy of MilanFondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

franco.valenza@unimi.it

Percorso “DCD-donor”

ACC sul territorio

Trasferimento in PS

Diagnosi di morte

Percorso di donazione “polmone”

Strategia di preservazione nel cadavereValutazione qualità organo – ricondizionamento

“Open lung strategy”

Collasso InflazioneOssigenzione

“Open lung strategy”

“Ex-vivo Lung Perfusion - EVLP”

EVLP Trapianto

11.30 15.30 19.30 23.30 4.30 19.30

DecessoConsenso

Prelievo

Percorso “DCD-donor”

1 novembre 2014

Strategia di preservazione nel cadavere

sempliceesportabile

a basso costo

Ex-Vivo Lung Perfusionvalutare

ricondizionaremigliorare

Percorso “DCD-donor”

... It is feasible!

12 Potenziali DCD / anno

AREU-118 Milano, Monza-Brianza (aprile-giugno 2014)

1113 Arresto Cardiocircolatorio

783 Trattamento Arresto

234 Trasferimento in Pronto soccorso

30 Età, HIV-HCV, neoplasia

…. sopravvivenza 50%…. rate idoneità EVLP 20%

??????

12 Potenziali DCD / anno

Milano

12 Potenziali DCD / anno