PowerPoint Presentation · •Objective 1. Review fundamentals of organ donation –process and...

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



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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43%

62%

0 20 40 60 80 100

MD OPO


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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


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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


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DonorCenter A

Center B

Center C

Center B

Center D

Center A



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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16 To Be Determined

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


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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


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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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%


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

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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

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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PowerPoint Presentation · •Objective 1. Review fundamentals of organ donation –process and...

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