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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
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
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
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
Adapted from Orens et al,JHLT 2003;22:1183-1200
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
Adapted from Orens et al,JHLT 2003;22:1183-1200
TABLE V SUMMARY OF LITERATURE FOR DONOR LUNG ISCHEMIC TIME (ISCHEMIC TIME >5 TO 6 HOURS)
Reference n Design Outcome (survival)
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
Adapted from Orens et al,JHLT 2003;22:1183-1200
TABLE VII SUMMARY OF LITERATURE FOR DONOR SMOKING HISTORY
Reference n Design Outcome (survival)
Gabbay et al (1999) 5/64 Retrospective review No adverse affect
Sundaresan et al (1995) 9/44 Retrospective review No adverse affect
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.
Adapted from Orens et al,JHLT 2003;22:1183-1200
Marginal Donors
Is there other Evidence?
Marginal Donors
Is there other Evidence?
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
Is there other Evidence?
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
.
Adapted from Orens et al,JHLT 2003;22:1183-1200
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
Adapted from Orens et al,JHLT 2003;22:1183-1200
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
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
103 = 13.7 kPa 463 = 61.7 kPa
Kaplan-Meier survival curves
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
Conclusion
Aggressive organ procurement management
of donors initially considered unacceptable
may increase the number of lungs
available for transplantation
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
Marginal Donors
SMOKING?
TABLE VII SUMMARY OF LITERATURE FOR DONOR SMOKING HISTORY
Reference n Design Outcome (survival)
Gabbay et al (1999) 5/64 Retrospective review No adverse affect
Sundaresan et al (1995) 9/44 Retrospective review No adverse affect
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.
Adapted from Orens et al,JHLT 2003;22:1183-1200
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
Avlonitis et al, EJCTS 2003; 24:601-607
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
Avlonitis et al, EJCTS 2003; 24:601-607
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