powerpoint presentation · •objective 1. review fundamentals of organ donation –process and...
TRANSCRIPT
2/17/2020
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Organ Donor
Management:2020 Update
Lee E. Morrow, MD, MSc
Professor of Medicine
Professor of Pharmacy Practice
Creighton University
CONFLICTS OF INTEREST: NONE!
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I HAVE BEEN THE MEDICAL DIRECTOR FOR NORS/LIVE ON NEBRASKA SINCE 2014
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THERE ARE NO STUPID QUESTIONS – INTERRUPT ME AT ANY TIME
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OBJECTIVES
• Objective 1. Review fundamentals of organ donation – process and regulations – under the UNOS system.
• Objective 2. Understand the importance of successfully achieving the donor management goals.
• Objective 3. Introduce ex vivo lung perfusion as an option to increase lung donation.
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ORGAN DONATION IS THE PROVERBIAL ‘THREE-LEGGED STOOL’
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LEG 1: TRANSPLANT CENTERS
LEG 2: ORGAN PROCUREMENT
ORGANIZATIONS
LEG 3: UNITED NETWORK FOR ORGAN
SHARING
(UNOS)
ORGAN PROCUREMENT ORGANIZATIONS (OPO)
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HOW DOES DONATION WORK? PART 1 = RECIPIENT SELECTION
Center A
Center B
Center C
Center B
Center D
Center A
People NeedingLiver Transplants
People NeedingLung Transplants
10ALSO LISTS FOR KIDNEYS, HEARTS, PANCREAS, SMALL BOWEL…EACH AT MULTIPLE TRANSPLANT CENTERS
HOW LONG IS THE WAIT?
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HOW DOES DONATION WORK? PART 2 = DONOR IDENTIFICATION/SELECTION
DonorCenter A
Center B
Center C
Center B
Center D
Center A
People NeedingLiver Transplants
People NeedingLung Transplants
OPO
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UNDERSTANDING THE APPROACH PROCESS
What is considered an “approach” for donation?
• The initial mention of the word “donation” to a family is considered an approach
Who can approach?
• Per CMS, the individual who initiates request to the family MUST be an OPO representative or a designated requestor who has been trained by the OPO
• It has to be done right for things to work
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UNDERSTANDING THE APPROACH PROCESS
DO NOT TALK TO FAMILIES ABOUT
DONATION IN THE ACUTE SETTING. EVER.
EVEN IF THEY ASK
YOU ABOUT IT.
WHY?!? 14
RATIONALE #1 FOR THIS RESTRICTIVE APPROACH PROCESS
43%
0 20 40 60 80 100
MD
Gortmaker, et.al. J Transplant Coordination. 1998;8:210
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RATIONALE #1 FOR THIS RESTRICTIVE APPROACH PROCESS
43%
62%
0 20 40 60 80 100
MD OPO
Gortmaker, et.al. J Transplant Coordination. 1998;8:210
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RATIONALE #1 FOR THIS RESTRICTIVE APPROACH PROCESS
43%
62%
72%
0 20 40 60 80 100
MD
OPO
MD + OPO
Organ donation consent rates are highest when hospital staff and the OPO approach collaboratively
Gortmaker, et.al. J Transplant Coordination. 1998;8:210
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• This is probably the WORST time in most of these individuals’ lives
• We have a duty to prevent inflicting further emotional distress for these families during their time of extreme vulnerability
• Imagine a well-intended provider brings up organ donation
• The family ‘rallies’ as now something good might come from this tragedy
• Only to have the OPO determine that they are not eligible to donate…
• On more than one occasion we have seen this additional – but unintentional –emotional burden inflicted on grieving families
RATIONALE #2 FOR THIS RESTRICTIVE APPROACH PROCESS
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DonorCenter A
Center B
Center C
Center B
Center D
Center A
People NeedingLiver Transplants
People NeedingLung Transplants
OPO
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HOW DOES DONATION WORK? PART 3 = ORGAN ALLOCATION
• Management depends on the ‘flavor’ of donation: DBD or DCD
• With DBD
• The donor is legally dead
• Cadaver with ongoing support to maintain viability of organs for donation
• OPO can manage independently without conflict of interest
• With DCD
• The potential donor is still alive
• Would be a conflict of interest for the OPO to manage them as actions could be perceived as hastening death
THE OPO MANAGEMENT ROUTINE
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CARE IS PROTOCOLIZED
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1. MAP 60-110 mm Hg
2. HR 60-120 beats/min
3. CVP 4-12 cm H2O
• 4-8 cm H2O if a potential lung donor
4. LVEF ≥50%
5. Arterial pH 7.30-7.50
6. P:F ratio ≥300
DONOR MANAGEMENT GOALS (DMG)
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7. Serum Na ≤155 mEq/L
8. Serum glucose 60-180 mg/dL
9. UOP 0.5-3.0 cc/kg/hr
10.Temperature 36.0-37.5°C
11.Other electrolytes “balanced”
12.“Normal” hematology
DONOR MANAGEMENT GOALS (DMG)
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Malinoski et al. J Trauma. 2011;71(4):990-996.
Bottom LineMeeting the DMGs
(any eight or more) is associated with increased
organ recovery
LUNGS ARE THE ‘PROBLEM CHILD’ IN THE TRANSPLANT WORLD
Of the ‘life saving’ solid organ transplants (heart, lung, liver, kidney), the lungs:
Have the lowest rate of conversion
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Are least tolerant of ischemia
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LUNGS ARE THE ‘PROBLEM CHILD’ IN THE TRANSPLANT WORLD
Of the ‘life saving’ solid organ transplants (heart, lung, liver, kidney), the lungs:
Have the worst outcomes…
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…despite most intense immune suppression regimens
CONVENTIONAL WISDOM: WE HAVE A SUPPLY PROBLEM
Frequently Cited Remedies
1. Better Management
2. More registered donors
• Awareness• Opportunity
3. Liberalize criteria for acceptance/utilization:
• DCD lungs• Use marginal donor lungs• EVLP
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SO IT MAKES SENSE TO HAVE THE ‘BEST’ PEOPLE MANAGING DONORS
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NOT SURPRISING…
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HIGH-DOSE NALOXONE – CHAPTER 1
• Observational, historic data suggested that high-dose naloxone (Narcan) improved noncardiogenic pulmonary edema in addition to reversing hypoventilation in opiate overdose
• Phenomenon was observed in a cluster of donors who had overdosed in the wake of the ‘Just Say No’ arrests
• Therapeutic high-dose naloxone was then considered for use in brain-dead donors with marginal pulmonary function
• Prospective study of 19 consecutive potential lung donors who were declared brain dead potential: all were given 8-10 mg naloxone
• O2 challenge before vs. immediately after naloxone was 329 vs. 363 (P=NS)
• O2 challenge before vs. 6 hours after was 329 vs. 413 (P<0.01)
• No consideration of lung recruitment efforts during these 6 hours
Eagan et al. Prog Transplant. 2009;19;267. 29
HIGH-DOSE NALOXONE – CHAPTER 2
• Subsequent multi-center, randomized, placebo-controlled, clinical trial
• 199 lung-eligible, brain dead donors: 8 mg naloxone (n=98) or saline placebo (n=101)
• Primary outcome was change in PF ratio from baseline to final ABG
• 81 vs. 80 (p=0.68)
• No improvement in rate of lung transplantation
Dhar et al. Transplantation. 2018. 30
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THE NUMBER OF PEOPLE WAITING FOR A LUNG TRANSPLANT CONTINUES TO GROW
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IS THE LUNG SHORTAGE A SUPPLY PROBLEM OR A DEMAND PROBLEM?
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1. The current system has “perverse incentives”
• Higher survival rates are rewarded
• No reward for high utilization rates
• No adjustments for marginal lung utilization
2. “Key players have conflicting interests”
• Transplant surgeons have conflicts of commitment (non-transplant cases)
• Urgency of other recipients may trump lung allocation
• Fixing these flaws will overcome the gap between the numbers of candidates and recipients
HOWEVER, SUB-PAR OPO PERFORMANCE IS ALSO TO BLAME…
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NEW YORK ORGAN DONOR NETWORK: POSTER CHILD FOR BAD PERFORMERS
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NEW YORK ORGAN DONOR NETWORK
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Disconnect!
Although 95% of US adults support organ donation – only 48% are registered donors
LET’S AVOID THAT CONFLICT – AND DISTRACT OURSELVES WITH OTHER THINGS
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How about those Huskers?
Nebraska is 39th at 56%
AND THERE IS DRAMATIC VARIABILITY IN REGISTRATION RATES
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LET’S INCREASE THE DONOR POOL BY TARGETING MILLENIALS
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THE TIMES THE ARE A-CHANGIN’
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THE TIMES THE ARE A-CHANGIN’ – EX VIVO LUNG PERFUSION (EVLP)
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NOT ALL EVLP IS EXACTLY THE SAME THOUGH…
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TRANSMEDICS: OCS LUNG®PROLONGING ISCHEMIC TIME (3/22/18)UTILIZING MARGINAL ORGANS (11/6/19)
XVIVO PERFUSION: XPS®UTILIZING MARGINAL ORGANS (4/29/19)
THE XVIVO PERFUSION XPS
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THE BASIC IDEA
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Nationwide, 75% of
lungs pursued by
OPOs for potential
transplantation do
NOT get used for a
host of reasons
Perhaps we could take
some suboptimal lungs and:
(1) optimize them ex vivo
(2) demonstrate that they
function acceptably or
(3) buy time to resolve
logistical issues
HUGE potential to increase
the number of lungs used
for transplant
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THE PROCESS STARTS WITH SOME ‘UNLOVED’ LUNGS
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Therefore, the study site
transplant centers request
documentation from the
OPO that the donor lungs
would not otherwise be
used direct to transplant for
each EVLP case
Alternatively, an OPO
medical director can refer
lungs for EVLP to LBE
directly
if a study site transplant center
is unable to accept an offer:
the OPO would then continue
allocation to a study site while
EVLP is in progress
To be referred as an EVLP
lung, the OPO must determine
that allocation efforts would not
result in a standard direct to
transplant from the donor given
unique circumstances of each
case
OPOTRANSPLANT
CENTEROPO
OR
POSSIBLE REASONS LUNGS WOULD NOT BE USED FOR STANDARD TRANSPLANT
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Match run
exhauste
d
Other
Logistical
challenge
s
Donation after
Circulatory Death
(DCD)
OR declineRecipient
availability
DONOR LUNG EXCLUSION CRITERIA
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The donor lung has confirmed
pneumonia and/or persistent
purulent secretions identified
via bronchoscopy prior to donor
lung excision
Any purulent secretions not
considered persistent identified
in the donor lung prior to
excision that do not clear by the
hour 3 assessment of EVLP
The donor lung has
significant mechanical
lung injury or trauma
The donor has HIV or
active hepatitis C
The cold ischemic time (CIT),
starting at aortic cross
clamp/initial flush, required to
transport the lung from the
donor site to the start
of EVLP at the sponsor facility
will be >10 hrs
The donor lung has
confirmed evidence of
aspiration
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STANDARDIZED FORM
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Digital Print
STUDY SITES
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Transplant Center
Study Sites16
Mayo Clinic Florida
University of Maryland
University of Pittsburgh
Loyola University Chicago
Cleveland Clinic
University of Michigan
Duke University
Inova Fairfax
Washington University St. Louis
Johns Hopkins
New York University
Indiana University
Vanderbilt University
Tampa General
Newark Beth Israel
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THE HIGH LEVEL OVERVIEW OF THE PROCESS
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Lungs declined by
study center. End
evaluation. Lungs will
not be transplanted
and will be disposed
of per OPO directions.
Lungs accepted by
study center for
transplant and re-
packaged according
to OPTN policy for
transport to study
center
Donor lungs
referred by study
center OR OPO
medical director to
sponsor for EVLP
Standard lung
recovery by lung
surgeon: transport
lungs to EVLP
facility
EVLP for at least 3
and no more than
6 hours withhourly
and as requested
lung data collection
Lung data relayed
to study center for
transplant suitability
evaluation
PROCESS FOR ACCEPTANCE OR
DECLINE
OF DONOR LUNGS FOR EVLP
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Decision
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THIS IS STILL INVESTIGATIONAL! STUDY OBJECTIVES
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PRIMARY
OBJECTIV
E
The objective of this study is to evaluate the safety and effectiveness
of the Centralized Lung Evaluation System (CLES) in enabling
evaluation of potential donor lungs not otherwise used for transplant
into subjects with end stage, survival-limiting lung disease in need of
lung transplantation. This will be accomplished by evaluating
subject survival at the later of 6 months or hospital discharge
post-transplant.
MONTHS6SUCCESS
CRITERIO
N
SURVIVALAT88.4%
The data will also be
collected on patients
enrolled in a
contemporaneous control
group to provide context
for EVLP results.
STUDY DESIGN AND PLAN
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SAMPLE SIZE
=
186
SUBJECTS
SPLIT INTO
2 GROUPS:
UNBLINDED,
NON-
RANDOMIZED
PIVOTAL
STUDY
INCLUDES
MALE AND
FEMALES
RECIPIENTS >18
YEARS OF AGE
EVLPGROUP
N=93
(EVLP to transplant
through standard OPTN matchrun system)
CONTROL
GROUP N=93
(non-EVLP; transplant
through standard OPTN matchrun system)
Control group will be selected to
best match the EVLP groupwith respect to the following
criteria:
» SLT vs DLT
» ECMO status at time
of lung allocation/offer
» Lung Allocation Score
Disease Diagnosis
Group
(LASDDG). Assigned
according to OPTN Policy
10.1.F.i
into one of four groups:
GROUP A: Obstructive Lung Disease
GROUP B: Pulmonary Vascular Disease
GROUP C: Cystic Fibrosis
or Immunodeficient
Disorders
GROUP D: Restrictive Lung Disease
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P R OTOC O L R E VIE W: S TUDY OB J E C TIVE S
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0H
48H
24H
72H
SECONDAR
Y
OBJECTIVE
S
E valuation of s afety in subjects receiving a lung transplant where the lung(s)
has/have been perfused via the C entralized L ung E valuation S ystem (C L E S ) by
assessment of the following:
P G D S core (G rades 0-3) measured at
S ubject s urv ival at:
Time to firs t
ex tubation
R ate of E C MO
us e pos t-
trans plant
IC U L eng th Of
S tay (L OS )
Measured as total
number of days in the
hospital prior to firs t
hospital discharge post-
transplant
Hos pital L OS
post-transplant
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Assessment of the
overall safety of T E S
lung
transplants during subject’s
participation in the s tudy,
as reported through
adverse events (AE s )
R ate of C hronic
L ung Allog raft
D ys func tion (C L AD)
R ate of res piratory
failure
FE V 1 values at fo llow-
up vis its
T he data will als o be collected on patients enrolled in a contemporaneous control group to provide context for E V L P res ults .
Measured as total number
of days post-transplant in
the IC U until firs t hospital
discharge, inclus ive of IC U
readmiss ions during that
hospitalization
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DAYS DAYS YEAR
P R OTOC O L R E VIE W: S TUDY OB J E C TIVE S
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E valuate the effec tivenes s of the E VL P assessment by the following metrics:
Total pres ervation
time (T PT )
Inc reas ed us e of
donor lung sUtilization rate
SECONDARY OBJECTIVES(CONTINUE D)
Measured by the numberof lungs referred for EVL Pand accepted for transplantation at a Study Center without the use ofEVL P
Defined as elapsed time between donor aortic cross clamp at procurement and placement of the first anastomotic suture at transplant (for 1st lung)
For lungs that wouldotherwise not be useddirect to transplantform the donor
T he data will als o be collected on patients enrolled in a contemporaneous control group to provide context for E V L P res ults .
ME THOD OF A S S IG NING PATIE NT S TO INTE R VE NTIO N
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All patients who have provided informed consent are screened and eligibility asses s ed according to inclus ion/exclus ioncriteria
At the time of lung allocation, the determination is madewhether the lung qualifies forEVL P
After at leas t 1 EV L P subject has been enrolled, Investigators are notified that a control group slot is available at their studycenter
Identification of potential control subjec ts is doneprospectively
Enrollment commenc esupon lung transplantation
A control subject may be enrolled only after an EVL P subject has been enrolled at that specific s tudy center
A control subject must be enrolled if there are three unmatched EVL P subjec ts at any time during the study
In order that no more than two-thirds of the subjects enrolled (93 subjects per group) will have received eitherSLT or DLT, study centers will be kept informed regarding the numbers and types of transplants that have taken place at all studysites
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E VL P A C C E P TA NC E C R ITE R IA
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A ll donor lung s preserved on C L E S mus t meet at leas t one of the two s tandard clinical criteria for transplant at final assessment on the C L E S:
A ny decis ion to turn down lung s after the lungs have been retrieved, preserved, and assessed on C L E S should be done with notification to the site principal investigator and the clinical reason(s)for turning down the donor lung for transplant shall be documented.
» Final CL E S PaO2/FiO2 ratio of ≥300 at the end of E VL P ; OR
» PAP, PVR , and PAWP trends stable or <20% worsening from baseline measurements taken at hour one compared to measurements taken at the end of E VL P ; AND
» Study site physician must be clinically satisfied with the lung evaluation, and if not, the reason for refusal must be listed.
R E C IP IE NT INC L US IO N C R ITE R IA
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18 years of age orolder
Patient actively awaiting a single or bilateral lung transplant
Patient or patient’s representative provides informed consent for participation inthe study prior to participating in any study-related assessments or procedures
Patient matches with and undergoes a transplant witha donor lung
R E C IP IE NT E X C L US IO N C R ITE R IA
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Patientslisted for same side lung re-transplantation
Patients listed formultiple-organ transplantation including lung and any other organ
Patients listed for live donor lobar transplant
Patients positive for human immu-nodeficiency virus (HIV) or Burkholderia cepacia infection
Patient receives a standard of care (non-EVLP ) lung transplant but does not match to an EVLP subject basedonthe criteriafor controlmatching
Participating in another interventional trial
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P R OTOC O L R E VIE W: S TUDY OB J E C TIVE S
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PRIMARY
OBJECTIV
E
T he objective of this study is to evaluate the s afety and effec tivenes s
of the C entralized L ung E v aluation S ys tem (C L E S ) in enabling
evaluation of potential donor lungs not otherwise used for transplant
into subjects with end stage, survival-limiting lung disease in need of
lung transplantation. T his will be ac c omplis hed by ev aluating
s ubjec t s urv iv al at the later of 6 months or hos pital d is c harg e
pos t-trans plant.
Feas ibility analys is : 6-month surv ival is 93.6% vs . national averag e of 93.4%
MONTHS6SUCCESS
CRITERIO
N
S UR VIVALAT88.4%
T he data will als o be collected on patients enrolled in a contemporaneous control group to provide context for E V L P res ults .
THE TR A NS ME DIC S OC S L UNG
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THE TR A NS ME DIC S OC S L UNG
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TR A NS P L A NT C E NT E R S WITH TR A NS ME DIC S OC S L UNG
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R E C E NT LY S P OTTE D ON X VIVO’S WE B S IT E …
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OC TOB E R 9, 2019 – THE C A NA DIA N P E R S P E C TIVE ON E VL P F OR MA R G INA L L UNG S
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WHAT A R E THE C OS T IMP L IC ATIO NS ?
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WHAT A R E THE C OS T IMP L IC ATIO NS ?
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HOW MUC H WOUL D Y OU B E WIL L ING TO PAY ?
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• O P O s charge transplant centers an ‘acquis ition fee’ for each organ that is accepted for transplantation
• As nonprofits, charges = costs• Kidney $36,000• Heart $38,000• Liver $34,000• Single Lung $37,000• Bilateral Lungs $47,000• Pancreas $35,000• Small Intestine $24,000
?
HOW MUC H WOUL D Y OU B E WIL L ING TO PAY ?
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• O P O s charge transplant centers an ‘acquis ition fee’ for each organ that is accepted for transplantation
• As nonprofits, charges = costs• Kidney $36,000• Heart $38,000• Liver $34,000• Single Lung $37,000• Bilateral Lungs $47,000• Pancreas $35,000• Small Intestine $24,000
NOT DONOR -R E L AT E D, B UT S TIL L INTR IG UING …
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QUE S T IONS ?
E VL P TO INC R E A S E THE DONOR P OOL
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