PICO
Population: Adults and children who are receiving an organ transplantation in any setting
Intervention: Organ retrieved from a donor who has had CPR (e.g. donor dies on ICU after initial
successful CPR , or donation after unsuccessful CPR)
Comparison: Organ retrieved from a donor who did not have CPR
Outcomes: Survival rates, Complication Rate Graft survival in Recipient
o Immediate graft function (no death in 30 days)
(Critical Outcome)
o 1-Year graft function
(Important Outcome)
o 5-Year graft function
(Important Outcome)
Literature Search
PubMed Search Strings
Date PubMed Search Completed
7/16/2014
(Outcome*[TIAB] OR "Treatment Outcome"[Mesh] OR surviv*[TIAB] OR "Survival Rate"[Mesh] OR
"Survival Analysis"[Mesh] OR reject*[TIAB] OR "Host vs Graft Reaction"[Mesh] OR
complication*[TIAB] OR "complications" [Subheading] OR "Postoperative Complications"[Mesh] or
fail*[TIAB] OR "Risk"[Mesh] OR "Delayed Graft Function"[Mesh] OR efficacy[TIAB] OR
efficacious[TIAB] OR safe*[TIAB] OR damag*[TIAB]) AND ("Tissue and Organ Harvesting"[Mesh] OR
"Tissue and Organ Procurement"[Mesh] OR "Organ Transplantation"[Mesh] OR “organ
transplant”[TIAB] OR "Tissue Donors"[Mesh:NoExp] OR donor*[TIAB] OR donat*[TIAB]) AND
(CPR[TIAB] OR "resuscitation"[Mesh] OR resuscitat*[TIAB] OR “chest compression”[TIAB] OR “chest
compressions”[TIAB] OR “heart massage”[TIAB] OR “cardiac massage”[TIAB] OR “cardiac
compression”[TIAB] OR “cardiac compressions”[TIAB] OR “thoracic compression”[TIAB] OR
“thoracic compressions”[TIAB] OR “basic life support”[TIAB) NOT (“animals”[Mesh] NOT
“humans”[Mesh]) NOT ("letter"[pt] OR "comment"[pt] OR "editorial"[pt] or Case Reports[ptyp])
747 results - June 27, 2014
Embase Search Strings
Date Embase Search Completed
7/16/2014
(Outcome*:ti OR 'treatment outcome'/exp OR surviv*:ti,ab OR 'survival rate'/exp OR 'survival'/de OR
reject*:ti,ab OR 'graft versus host reaction'/exp OR 'graft rejection'/exp OR complication*:ti,ab OR
'postoperative complication'/de or fail*:ti,ab OR 'risk'/de OR 'delayed graft function'/exp OR
efficacy:ti,ab OR efficacious:ti,ab OR safe*:ti,ab OR damag*:ti,ab) AND ('transplantation'/exp OR
“organ transplant”:ti,ab OR 'donor'/de or 'organ donor'/exp OR donor*:ti,ab OR donat*:ti,ab) AND
(CPR:ti,ab OR 'resuscitation'/exp OR resuscitat*:ti,ab OR 'heart massage'/exp or “chest
compression”:ti,ab OR “chest compressions”:ti,ab OR “heart massage”:ti,ab OR “cardiac
massage”:ti,ab OR “cardiac compression”:ti,ab OR “cardiac compressions”:ti,ab OR “thoracic
compression”:ti,ab OR “thoracic compressions”:ti,ab OR “basic life support”:ti,ab) NOT ('animal'/exp
NOT 'human'/exp) NOT ([editorial]/lim OR [letter]/lim OR 'case report'/de) AND [embase]/lim
1860 results - June 27, 2014
Cochrane Search Strings
Date Cochrane Search Completed
7/16/2014
(Outcome*:ti,ab OR [mh "Treatment Outcome"] OR surviv*:ti,ab OR [mh "Survival Rate"] OR [mh
"Survival Analysis"] OR reject*:ti,ab OR [mh "Host vs Graft Reaction"] OR complication*:ti,ab OR [mh
"Postoperative Complications"] or fail*:ti,ab OR [mh "Risk"] OR [mh "Delayed Graft Function"] OR
efficacy:ti,ab OR efficacious:ti,ab OR safe*:ti,ab OR damag*:ti,ab) AND ([mh "Tissue and Organ
Harvesting"] OR [mh "Tissue and Organ Procurement"] OR [mh "Organ Transplantation"] OR “organ
transplant”:ti,ab OR [mh ^"Tissue Donors"] OR donor*:ti,ab OR donat*:ti,ab) AND (CPR:ti,ab OR [mh
"resuscitation"] OR resuscitat*:ti,ab OR “chest compression”:ti,ab OR “chest compressions”:ti,ab OR
“heart massage”:ti,ab OR “cardiac massage”:ti,ab OR “cardiac compression”:ti,ab OR “cardiac
compressions”:ti,ab OR “thoracic compression”:ti,ab OR “thoracic compressions”:ti,ab OR “basic life
support”:ti,ab) NOT ([mh “animals”] NOT [mh “humans”])
27 Results - June 27, 2014
Considerations about outcomes:
For this review, we looked for data on organ procurement of major organs (heart, lung, liver, kidney,
intestine) and excluded data about procurement of tissues (skin, bone, cornea), because there has
never been concern about the effects of antecedent CPR on tissue donation.
In reviewing the articles, we identified two situations: procurement of organs from donors who had
survived CPR, but went on to reach brain death or withdrawal of life sustaining treatment in a
manner that would qualify for organ donation (CPR-donors), AND procurement of organs from
donors who had ongoing CPR that was failing to achieve return of pulses (uncontrolled non-heartbeating donors , NHBD, or uncontrolled Donation after Circulatory Death, DCD). The latter are
NHBD Maastricht Type 2 donors. We considered these two situations separately, because they are
physiologically, practically, and conceptually different.
We determined that outcomes for kidneys included specifically graft failure, because patients can
survive on hemodialysis after graft failure. For other organs, patient mortality was also considered
graft failure. However, the cause of patient death was often unclear and might have included other
causes (infection, bleeding, etc.). This makes the estimates conservative, but they are also more
meaningful from the perspective of the patient. Few papers tabulated organ failure resulting in retransplant, but we also would consider that as “graft failure” if it was noted.
We included articles that had (1) comparison of outcomes between target donors and other donors,
(2) outcomes of immediate graft function, 1 year or 5 year. In some papers, immediate graft
outcome was reported as “outcome at 30 days,” which captures the same intent: the organ initially
worked when placed in the recipient and after the immediate post-operative stabilization of the
recipient.
We noted the yield of organs per donor (the number of organs procured from each donor) in papers
where that was reported.
CPR –Donors
Heart Transplant
Study
N
With CPR
N
Without CPR
Immediate
Graft
Function
Adrie 2008
7
9
Ali 2007
38
566
97.4% vs.
92.2%
Hsu 1999
9
24*
100% vs. 88%
Orioles 2013
834
19872
“No
difference”
Quader 2013
1396
26370
95.2% vs.
94.7%
Sanchez25
579
“No
Lazaro 2010
difference”
Southerland
930
20453
“No
2013
difference”
*Hsu 1999: This comparison group was all “marginal donors.”
1 Year Graft
Function
5 year Graft
Function
75% vs. 75%
94.2% vs.
83.6%
“No
difference”
88.2% vs.
87.7%
“No
difference”
“No
difference”
75% vs. 29%
79.8% vs.
74.5%
“No
difference”
72.8% vs.
74.2%
“No
difference”
“No
difference”
Pediatric Heart Transplant
Study
Conway 2013
N
With CPR
N
Without CPR
1050
2095
Immediate
Graft
Function
-
1 Year Graft
Function
5 year Graft
Function
“No
“No
difference”
difference”
DeBegona
68
72
“No
“No
1993
difference”
difference”
Finfer 1996*
2
9
50% vs 67%
L’Ecuyer 2011
144
2082
94.% vs
86.3% vs.
77.6% vs.
94.3%
87.7%
78.8%
Orioles 2013
343
5184
“No
“No
“No
difference”
difference”
difference”
*Finfer 1996: Higher rate of missing follow up that in other studies because survey was used
Lung Transplant
Study
Castleberry
2013
Pilarczyk
2011
Orioles 2013
N
With CPR
N
Without CPR
457
457
22
164
552
13029
Immediate
Graft
Function
95% vs. 96%
1 Year Graft
Function
5 year Graft
Function
67% vs. 64%
7.4% vs. 9.0%
95.5% vs.
95.7%
“No
difference”
84.4% vs.
85.5%
“No
difference”
66.3% vs.
69.8%
“No
difference”
Immediate
Graft
Function
“No
difference”
1 Year Graft
Function
5 year Graft
Function
“No
difference”
“No
difference”
Pediatric Lung Transplant
Study
Orioles 2013
N
With CPR
N
Without CPR
105
2219
Kidney Transplant
Study
Adrie 2008
Mercatello
1988*
Orioles 2013
N
With CPR
N
Without CPR
29
30
79
113
4971
89349
Immediate
Graft
Function
80% vs. 58%
1 Year Graft
Function
5 year Graft
Function
97% vs. 95%
-
97% vs 89%
-
“No
“No
“No
difference”
difference”
difference”
*Mercatello 1988: Outcomes only reported to 7 days: cannot exclude delayed graft function
Pediatric Kidney Transplant
Study
N
With CPR
N
Without CPR
Immediate
1 Year Graft
5 year Graft
Graft
Function
Function
Function
Finfer 1996*
52
80
65% vs 66%
Orioles 2013
1070
13608
“No
“No
“No
difference”
difference”
difference”
*Finfer 1996: Higher rate of missing follow up that in other studies because survey was used
Liver Transplant
Study
Adrie 2008
Orioles 2013
N
With CPR
N
Without CPR
14
2897
43
54274
Immediate
Graft
Function
86% vs. ?
“No
difference”
1 Year Graft
Function
5 year Graft
Function
71% vs. 95%
“No
difference”
71% vs. 95%
“No
difference”
1 Year Graft
Function
5 year Graft
Function
“No
difference”
“No
difference”
Pediatric Liver Transplant
Study
Finfer 1996
Orioles 2013
N
With CPR
N
Without CPR
10
679
19
9171
Immediate
Graft
Function
70% vs. 58%
“No
difference”
Intestine Transplant
Study
Matsumoto
2008
Orioles 2013
N
With CPR
N
Without CPR
Immediate
Graft
Function
100% vs. 84%
1 Year Graft
Function
5 year Graft
Function
12
55
83% vs. 82%
-
13
479
“No
difference”
“No
difference”
“No
difference”
N
With CPR
N
Without CPR
1 Year Graft
Function
5 year Graft
Function
79
1211
Immediate
Graft
Function
“No
difference”
“No
difference”
“No
difference”
Pediatric Intestine Transplant
Study
Orioles 2013
Prior CPR in Donor compared with No Prior CPR for Graft Function
Patient or population: Any Patient with Organ Transplant
Settings: Any Organ Transplant
Intervention: CPR in Donor
Comparison: No CPR in Donor
Outcomes
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Heart
3230 CPR vs. 67,849 no CPR
(6 studies)
low
⊕⊕⊝⊝
Pediatric Heart
1607 CPR vs. 9,442 no CPR
(5 studies)
low
⊕⊕⊝⊝
-----------------------------------------1035 CPR vs. 13,654 no CPR
(3 studies)
-------------------------------low
⊕⊕⊝⊝
105 CPR vs. 2,219 no CPR
(1 study)
low
⊕⊕⊝⊝
--------------------Kidney
-----------------------------------------5,030 CPR vs. 89,541 no CPR
(3 studies)
-------------------------------low
⊕⊕⊝⊝
Pediatric Kidney
1122 CPR vs. 13,688 no CPR
(2 studies)
low
⊕⊕⊝⊝
--------------------Liver
-----------------------------------------2,911 CPR vs. 54,317 no CPR
(2 studies)
-------------------------------low
⊕⊕⊝⊝
689 CPR vs. 9,190 no CPR
(2 studies)
low
⊕⊕⊝⊝
--------------------Intestine
-----------------------------------------25 CPR vs. 534 no CPR
(2 studies)
-------------------------------low
⊕⊕⊝⊝
Immediate (7 studies), 1
year (6 studies), 5 year (6
studies)
Immediate (4 studies), 1
year (4 studies), 5 year (3
studies)
--------------------------------Immediate (3 studies), 1
year (3 studies), 5 year (3
studies)
Immediate (1 studies), 1
year (1 studies), 5 year (1
studies)
--------------------------------Immediate (2 studies), 1
year (2 studies), 5 year (2
studies)
Immediate (2 studies), 1
year (1 study), 5 year (1
study)
--------------------------------Immediate (2 studies), 1
year (2 studies), 5 year (2
studies)
Immediate (2 studies), 1
year (1 study), 5 year (1
study)
--------------------------------Immediate (2 studies), 1
year (2 studies), 5 year (1
study)
Pediatric Intestine
79 CPR vs. 1211 no CPR
(1 study)
very low
⊕⊝⊝⊝
--------------------Lung
Pediatric Lung
Pediatric Liver
Footnotes
Immediate (1 study), 1 year
(1 study), 5 year (1 study)
Uncontrolled Non-Heart Beating Donors / Uncontrolled Donation after
Circulatory Death (UDCD)
NHBD / UDCD Kidney Transplant
Study
Alonso 2005*
Casavilla 1995
N
With NHBD –
M2
100
22
N
(Control)
Immediate
Graft
Function
84% vs. 90%
95% vs. 100%
1025 (HBD)
17 (controlled
NHBD)
Moruzumi
4
10 (controlled 100% vs. 90%
2009
NHBD)
Nicholson
77
224 HBD / 49
90.9% vs.
2000
LD
97.3%/98%
*Alonso 2005: included Maastricht Type 1,2 and 4 DCD.
1 Year Graft
Function
5 year Graft
Function
79% vs. 83%
86% vs. 82%
70% vs. 72%
-
-
-
86% vs.
84%/95%
79% vs.
75%/78%
1 Year Graft
Function
5 year Graft
Function
17% vs. 50%
-
71% vs. 72%
18% vs. 38%
55% vs. 73%
-
-
NHBD / UDCD Liver Transplant
Study
Casavilla 1995
Fondevila
2012
Otero 2004
Tosuka 1999
N
With NHBD –
M2
6
34
20
4
N
(Control)
6 (controlled
NHBD)
538 (HBD)
40 (HBD)
4 (controlled
NHBD)
Immediate
Graft
Function
50% vs. 100%
100% vs.
100%
75% vs. 97%
25% vs. 100%
Prior CPR in Donor compared with No Prior CPR for Graft Function
Patient or population: Any Patient with Organ Transplant
Settings: Any Organ Transplant
Intervention: Uncontrolled NHBD Maastricht 2 in Donor
Comparison: Other Donor
Outcomes
Kidney
--------------------Liver
Footnotes
No of Participants
(studies)
Quality of the evidence
(GRADE)
203 NHBD M2 vs. 1325
HBD/controlled NHBD/ Living
Donors
(4 studies)
low
⊕⊕⊝⊝
-----------------------------------------64 NHBD M2 vs. 588
HBD/controlled NHBD
(4 studies)
Comments
Immediate (4 studies), 1
year (3 studies), 5 year (2
studies)
-------------------------------- --------------------------------Immediate (4 studies), 1
low
year (3 studies), 5 year (1
⊕⊕⊝⊝
studies)
Consensus on Science
Donors with Prior CPR
Two papers reported the mean yield of organs procured from donors who had been resuscitated by
CPR prior to donation was 3.9 (Faucher 2014) or 2.9 (Orioles 2013).
For the critical outcome of immediate graft survival, low quality evidence from non-randomized
studies did not detect any worse outcome when donors have had CPR and resuscitation for adult
hearts (3239 organs, 7 studies), pediatric hearts (557 organs, 4 studies), adult lungs (1031 organs, 4
studies), pediatric lungs (105 organs, 1 study), adult kidneys (5,000 organs, 2 studies), pediatric
kidneys (1122 organs, 2 studies), adult livers (2,911 organs, 3 studies), pediatric livers (689 organs,
2 studies), adult intestines (25 organs, 2 studies), and pediatric intestines (79 organs, 1 study)
For the important outcome of graft survival for 1 year, low quality evidence from nonrandomized studies did not detect any worse outcome when donors have had CPR and resuscitation
for adult hearts (3230 organs, 8 studies), pediatric hearts (1605 organs, 8 studies), adult lungs (1031
organs, 4 studies), pediatric lungs (105 organs, 1 study), adult kidneys (5,000 organs, 2 studies),
pediatric kidneys (1122 organs, 2 studies), adult livers (2,911 organs, 3 studies), pediatric livers (689
organs, 2 studies), adult intestines (25 organs, 2 studies), and pediatric intestines (79 organs, 1
study)
For the important outcome of graft survival for 5 years, low quality evidence from nonrandomized studies did not detect any worse outcome when donors have had CPR and resuscitation
for adult hearts (3230 organs, 8 studies), pediatric hearts (1537 organs, 8 studies), adult lungs (1031
organs, 4 studies), pediatric lungs (105 organs, 1 study), adult kidneys (5,000 organs, 2 studies),
pediatric kidneys (1122 organs, 2 studies), adult livers (2,911 organs, 3 studies), pediatric livers (689
organs, 2 studies), adult intestines (25 organs, 2 studies), and pediatric intestines (79 organs, 1
study)
Donors with ongoing CPR (uncontrolled on-heart beating donors or uncontrolled donation after
circulatory death)
Two papers reported the mean number of organs procured from donors with ongoing CPR was 1.5
(Fondevilla 2012) and 3.2 (Mateos-Rodriguez 2012)
For the critical outcome of immediate graft survival, low quality evidence from non-randomized
studies did not detect any worse outcome when organs were recovered from non-heart beating
donors with ongoing CPR compared to other types of donors for adult kidneys (203 organs, 4
studies) or adult livers (64 organs, 4 studies).
For the important outcome of graft survival for 1 year, low quality evidence from nonrandomized studies did not detect any worse outcome when organs were recovered from non-heart
beating donors with ongoing CPR compared to other types of donors for adult kidneys (199 organs, 3
studies) or adult livers (60 organs, 3 studies).
For the important outcome of graft survival for 5 years, low quality evidence from nonrandomized studies did not detect any worse outcome when organs were recovered from non-heart
beating donors with ongoing CPR compared to other types of donors for adult kidneys (177 organs, 2
studies) or adult livers (34 organs, 1 study).
Treatment Recommendation:
1. We recommend that all patients who have restoration of circulation after CPR and who
subsequently progress to death be evaluated for organ donation (strong recommendation, low
quality of evidence).
In making this recommendation, we consider the absence of any evidence of worse graft function
from donors with antecedent CPR, the desirability of providing more organs to waiting recipients,
and the absence of any risk to the donor. As in all organ donation, the function of the donated organ
determines whether procurement and transplantation proceed. Therefore, there is also precaution
to ensure the safety of the recipient.
2. We suggest that patients who fail to have restoration of circulation after CPR and who would
otherwise have termination of efforts be considered candidates for kidney or liver donation in
settings where programs exist (weak recommendation, low quality of evidence).
In making this recommendation, we consider the evidence that kidney grafts obtained from donors
with ongoing CPR can function at rates comparable to kidneys obtained from other donors, and that
recipients can safely tolerate delayed graft function that is common with kidneys obtained in this
manner. We also consider the immediate life-saving potential of liver grafts, which offsets the
potentially greater rate of long-term graft failure in livers obtained from donors with ongoing CPR.