How Marginal can the Marginal Donor Be?

How Marginal can the Marginal Donor Be?

J H DARK

Freeman Hospital

University of Newcastle

NUMBER OF LUNG TRANSPLANTS REPORTED BY YEAR AND PROCEDURE TYPE

5 7 36 78190

419

704

922

10871223

13581338145014601491

16281690

187919302071

23862448

2708

0

250

500

750

1000

1250

1500

1750

2000

2250

2500

2750

Nu

mb

er

of

Tra

ns

pla

nts

Bilateral/Double LungSingle Lung

ISHLTNOTE: This figure includes only the lung transplants that are reported to the ISHLT Transplant Registry. As such, this should not be construed as representing changes in the number of lung transplants performed worldwide.

2009

Number of solid organ donors and lung transplantations- UK

736703 716

697664

637 634609

37 4261 73 87

127159

200

93 96118

147120 116 112 110

0

100

200

300

400

500

600

700

800

900

2000-2001 2001-2002 2002-2003 2003-2004 2004-2005 2005-2006 2006-2007 2007-2008

Year

Nu

mb

er

HB donors

NHB donors

Lung transplants

UK Transplant

Up to 40% of donors yielding lungs for transplant in some parts of the World

Lung Transplant Referrals for CF

Freeman Hospital 1994-2004

D ie d on L ist1 23

W a iting24

T ra nsp lan ted1 5 0 (3 0 % )

A c tive L ist2 9 9 (6 0 % )

A sse ssm e nt1 57

N e ver A sse ssed36

C F re fe rra ls4 92

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5 6 7 8 9 10 11 12

Lung Transplantation for Cystic FibrosisActual Survival

Marginal Donors

Landmarks• Classical Criteria

Harjula et al JTCVS 1987; 94:874-880

Ideal lung donor selection criteriaAge < 55 yr

ABO compatibility

Clear chest radiograph

PaO2 (FiO2 100 % + 5 cm H2O PEEP) > 40 kPa (PaO2/FiO2)

Smoking < 20 pack-years

Absence of chest trauma

Lack of previous cardiopulmonary surgery

Absence of organisms on sputum Gram stain

Absence of purulent bronchoscopic secretionsAggressive management of lung donors classified as unacceptable: Excellent recipient survival one year after transplantation Straznicka, M et al., JTCVS August 2002, Volume 124, Number 2 250-258

Marginal Donors

Landmarks• Classical Criteria• Sudaresan et al “Successful outcome of lung

transplantation is not compromised by the use of marginal donor lungs”

JTCVS, 1995; 109:1075-79

Marginal Donors

Landmarks• Classical Criteria• Sudaresan et al “Successful outcome of lung

transplantation is not compromised by the use of marginal donor lungs”

JTCVS, 1995; 109:1075-79• Orens et al “A review of lung transplant donor

acceptability criteria”

JHLT 2003; 22:1183-1200

TABLE II SUMMARY OF LITERATURE FOR THE USE OF OLDER LUNG DONORS

n Design Outcome

Novick et al (1999) 284/5,052 Retrospective Decreased survival

Meyer et al (2000) 23/1,800 Retrospective No adverse affect on intermediate survival

Bhorade et al (2000) 9/52 Retrospective No adverse affect on ventilator time, hospital stay or hospital survival

Hosenpud et al (2001) 15,465 Retrospective Risk factor for 1- and 5-year mortality

.

Adapted from Orens et al,JHLT 2003;22:1183-1200

TABLE III SUMMARY OF LITERATURE FOR DONOR BLOOD GASES (PaO2/F1O2 <300)

n Study Design Outcome

Harjula et al (1987) 1 Case report Primary graft failure

Shumway et al (1994) 25 (1) Case series No adverse

affect

Sandaresan et al (1995) 6 Retrospective review No adverse affect


TABLE IV SUMMARY OF LITERATURE FOR ABNORMAL DONOR CHEST X-RAY

Reference n Design Outcome (survival)

Gabbay et al (1999) 39/64 Retrospective review No adverse affect

Sundaresan et al (1995) 39/44 Retrospective review No adverse affect

Bhorade et al (2000) 5/52 Retrospective review No adverse affect


TABLE V SUMMARY OF LITERATURE FOR DONOR LUNG ISCHEMIC TIME (ISCHEMIC TIME >5 TO 6 HOURS)


Snell et al (1996) 63/106 Retrospective review Reduced long term

Novick et al (1999) 5,052 Retrospective review No adverse affect of registry data except when older

donor age

Gammie et al (1999) 60/392 Retrospective review No adverse affect

Fiser et al (2001) 15/136 Retrospective review No adverse affect

Kshettry et al (1996) 8/83 Retrospective review No adverse affect


TABLE VII SUMMARY OF LITERATURE FOR DONOR SMOKING HISTORY




Bhorade et al (2000) 15/52 Retrospective review No adverse affect (average 36 pack-

years)

No differences in short-term outcome with regard to post-operative ventilation or oxygenation, nor long-term survival to 2.5 to 3 years.


Marginal Donors

Is there other Evidence?

Marginal Donors


Ware et al, (Lancet 2002) assessed 29 pairs of lungs rejected for use. 83% had no or mild pulmonary oedema, 74% had intact alveolar fluid clearance and 62% had normal histology

Marginal Donors


Fisher et al (Thorax 2004) assessed inflammatory markers in lungs not used for transplant. There was no difference in BAL IL8 or neutrophil counts in the excluded lungs.

Trend towards more infection in used lungs

Marginal Donors

What is New?

Where are we in 2010?

What are the limits?

Marginal Donors

AGE

TABLE II SUMMARY OF LITERATURE FOR THE USE OF OLDER LUNG DONORS

n Design Outcome

Novick et al (1999) 284/5,052 Retrospective Decreased survival

Meyer et al (2000) 23/1,800 Retrospective No adverse affect on intermediate survival

Bhorade et al (2000) 9/52 Retrospective No adverse affect on ventilator time, hospital stay or hospital survival

Hosenpud et al (2001) 15,465 Retrospective Risk factor for 1- and 5-year mortality

.


ADULT LUNG TRANSPLANTS (1/1995-6/2001) Risk Factors for 1 Year Mortality

Donor Age

0

0.5

1

1.5

2

10 15 20 25 30 35 40 45 50 55 60Donor Age

Od

ds

of

1 Y

ear

Mo

rtal

ity

p = 0.0005

ADULT LUNG TRANSPLANTS (1/1995-6/1997) Risk Factors for 5 Year Mortality

Donor Age

0

0.5

1

1.5

2

2.5

3

10 15 20 25 30 35 40 45 50 55 60Donor Age

Od

ds

of

5 Y

ear

Mo

rtal

ity

p < 0.0001

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%1

98

2

19

84

19

86

19

88

19

90

19

92

19

94

19

96

19

98

20

00

20

02

% o

f T

ran

sp

lan

ts

0-10 11-17 18-35 36-49 50-59 60+

0

5

10

15

20

25

30

35

Me

an

do

no

r a

ge

(y

ea

rs)

Mean Age

HEART TRANSPLANTS: Donor Age by Year of Transplant

0

5

10

15

20

25

30

35

40

45

50

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Years

Me

an a

ge

(ye

ars)

MEAN AGE OF CARDIAC DONORS IN THE UK, 1990 - 2002

0

10

20

30

40

50

60

70

80

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Years

Ca

us

e o

f d

ea

th

intracranial

trauma

Cause of Death of all Organ Donors(%) UK1989-2002

Marginal Donors

OXYGENATION

TABLE III SUMMARY OF LITERATURE FOR DONOR BLOOD GASES (PaO2/F1O2 <300)

n Study Design Outcome

Harjula et al (1987) 1 Case report Primary graft failure

Shumway et al (1994) 25 (1) Case series No adverse

affect

Sandaresan et al (1995) 6 Retrospective review No adverse affect


No Lower limit defined from the literature

From Luckraz et al JHLT 2005;24:470-473

Marginal Donors

OXYGENATION

Luckraz et al JHLT 2005;24:470-473

350 patients, all paired lungs, one institution

Higher 30 day mortality

No overall increase

But 300 were HLTx,

Ischaemic times c 3hrs

Aggressive management of lung donors classified as unacceptable: Excellent

recipient survival one year after transplantation

Straznicka, M et al.JTCVS August 2002, Volume 124,

Number 2 250-258

Division of Cardiothoracic Surgery, University of California, Davis Medical

Centre, Sacramento

Hypothesis

Donor lungs with unacceptable PaO2/FiO2 ratios (<20 kPa) can be made acceptable with aggressive management and that 30-day and 1-year recipient outcomes with these lungs would not be significantly different than outcomes of recipients with traditionally ideal lungs

Aggressive management of lung donors classified as unacceptable: Excellent recipient survival one year after transplantation Straznicka, M et al., JTCVS August 2002, Volume 124, Number 2 250-258

Results of OPO management


103 = 13.7 kPa 463 = 61.7 kPa

Kaplan-Meier survival curves


Conclusion

Aggressive organ procurement management

of donors initially considered unacceptable

may increase the number of lungs

available for transplantation


Marginal Donors

SMOKING?

TABLE VII SUMMARY OF LITERATURE FOR DONOR SMOKING HISTORY




Bhorade et al (2000) 15/52 Retrospective review No adverse affect (average 36 pack-

years)

No differences in short-term outcome with regard to post-operative ventilation or oxygenation, nor long-term

survival to 2.5 to 3 years.


Marginal Donors

SMOKING?

Oto et al Transplantation 2004; 78:599-606

Significant early effect on oxygenation, ventilation time, and hospital stay, particularly for current and heavy dose smokers

Marginal Donors

SMOKING?

Oto et al Transplantation 2004; 78:599-606

Significant early effect on oxygenation, ventilation time, and hospital stay, particularly for current and heavy dose smokers

Almost half donors fell into the high-risk category

Marginal Donors

INFECTION?

Marginal Donors

INFECTION?

A positive donor gram stain does not predict outcome following lung transplantation

Weill et al JHLT 2002; 21:555-558

Marginal Donors

INFECTION?

A positive donor gram stain does not predict outcome following lung transplantation

Weill et al JHLT 2002; 21:555-558

Bacterial colonisation of the donor lower airways is a predictor of poor outcome in lung transplantation

Avlonitis et al, EJCTS 2003; 24:601-607

Marginal Donors

Bacterial colonisation of the donor lower airways is a predictor of poor outcome in lung transplantation


115 patients, donor BAL cultured

46% positive culture

Longer ventilation, ITU, hospital stay for recipients with bacterially infected donors

Worse short and log-term outcome

No increase in BOS in one-year survivors

Total Marginal Organs

52%Marginal

Mean duration of Ventilation

0

20

40

60

80

100

120

140

Marginal Non-marginal

Re-intubated (%)

0

5

10

15

20

Marginal Non-marginal0

5

10

15

20

25

30

2000 2001 2002 2003 2004

Tracheostomy

0

5

10

15

20

25

30

Marginal Non-marginal0

5

10

15

20

25

30

35

40

2000 2001 2002 2003 2004

Transplantation 2006;82:1273-9

Marginal Donors

Conclusions

Many indicators of “Marginality” have a price, at least in terms of early dysfunction, and eventually overall survival

These risks, minimised by better donor care and improved post-op management, are still worth taking for our recipient population

Marginal Donors

Conclusions

Many indicators of “Marginality” have a price, at least in terms of early dysfunction, and eventually overall survival

These risks, minimised by better donor care and improved post-op management, are still worth taking for our recipient population

Who receives the marginal organ is unresolved

THE

END

How Marginal can the Marginal Donor Be?

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