Annals of Neurology,
Journal Year:
2024,
Volume and Issue:
95(6), P. 1035 - 1039
Published: March 19, 2024
Normothermic
regional
perfusion
(NRP)
has
recently
been
used
to
augment
organ
donation
after
circulatory
death
(DCD)
improve
the
quantity
and
quality
of
transplantable
organs.
In
DCD‐NRP,
withdrawal
life‐sustaining
therapies
cardiopulmonary
arrest,
patients
are
cannulated
onto
extracorporeal
membrane
oxygenation
reestablish
blood
flow
targeted
organs
including
heart.
During
this
process,
aortic
arch
vessels
ligated
restrict
cerebral
flow.
We
review
ethical
challenges
whether
brain
is
sufficiently
reperfused
through
collateral
circulation
allow
reemergence
consciousness
or
pain
perception,
resumption
cardiac
activity
nullifies
patient's
prior
determination,
specific
authorization
for
DCD‐NRP
required.
ANN
NEUROL
2024;95:1035–1039
Liver Transplantation,
Journal Year:
2023,
Volume and Issue:
unknown
Published: April 12, 2023
In
situ
abdominal
normothermic
regional
perfusion
(A-NRP)
has
been
used
for
liver
transplantation
(LT)
with
donation
after
circulatory
death
(DCD)
grafts
in
Europe
excellent
results;
however,
adoption
of
A-NRP
the
United
States
lacking.
The
current
report
describes
implementation
and
results
a
portable,
self-reliant
program
States.
Isolated
an
extracorporeal
circuit
was
achieved
through
cannulation
abdomen
or
femoral
vessels
inflation
supraceliac
aortic
balloon
cross-clamp.
Quantum
Transport
System
by
Spectrum
used.
decision
to
use
livers
LT
made
assessment
perfusate
lactate
(q15min).
From
May
November
2022,
14
procurements
were
performed
our
transplant
team
(N
=
11
LT,
N
20
kidney
transplants,
1
kidney-pancreas
transplant).
median
run
time
68
minutes.
None
recipients
had
post-reperfusion
syndrome,
nor
there
any
cases
primary
nonfunction.
All
functioning
well
at
maximal
follow-up
zero
ischemic
cholangiopathy.
feasibility
portable
that
can
be
Excellent
short-term
post-transplant
both
kidneys
procured
from
A-NRP.
The American Journal of Bioethics,
Journal Year:
2024,
Volume and Issue:
24(6), P. 4 - 15
Published: June 2, 2024
Organ
donation
after
the
circulatory
determination
of
death
requires
permanent
cessation
circulation
while
organ
brain
irreversible
functions.
The
unified
brain-based
connects
and
criteria
for
in
as
follows:
systemic
causes
which
perfusion
function.
relevant
that
must
cease
is
to
brain.
Eliminating
from
donor
ECMO
circuit
thoracoabdominal
NRP
protocols
satisfies
but
only
if
complete
can
be
proved.
Despite
its
medical
physiologic
rationale,
remains
inconsistent
with
Uniform
Determination
Death
Act.
Transplantation,
Journal Year:
2023,
Volume and Issue:
107(8), P. 1650 - 1654
Published: May 12, 2023
The
brain-based
determination
of
death
("brain
death")
is
now
widely
accepted
throughout
the
world.
It
states
that
irreversible
cessation
brain
functions
fundamental
criterion
for
human
death.
recent
World
Brain
Death
Project
provided
a
comprehensive
cataloguing
all
aspects
including
its
medical
and
legal
acceptance
world.1
Organ
donation
after
(DBDD)
currently
accounts
majority
multiorgan
donations
internationally.
circulatory
(DCDD)
has
grown
worldwide
since
Institute
Medicine
United
States
endorsed
practice
controlled
DCDD
in
20002
US
national
conference
on
2005
standardized
practice.3
are
expanding
but
remain
fewer
than
number
DBDD
donations.
donor
requires
permanent
absence
systemic
circulation.
When
circulation
absent,
ceases.
essential
feature
unified
concept
produces
neuronal
perfusion
resulting
functions.
Thus,
by
criteria
consistent
with
neurologic
criteria.
In
situ
normothermic
regional
(NRP)
emerging
as
component
organ
recovery
procedures
DCDD.
Controlled
practiced
hospitalized
patients
planned
withdrawal
life-sustaining
therapy
(WLST).
NRP
uses
extracorporeal
membrane
oxygenation
to
reestablish
specific
regions
body
following
determination.
reestablished
may
be
restricted
abdominal
cavity
(A-NRP)
or
also
include
thoracic
(TA-NRP).
reportedly
improves
utilization
recipient
outcomes
comparable
those
organs
from
donors,4,5
it
raises
complex
medical,
ethical,
questions
must
resolved.6-8
protocols
This
situation
principal
question
NRP:
if
resumption
contradicts
conditions
declaration,
how
can
declared
dead
circulation?
use
resolves
dilemma
clarifying
relevant
cease
brain.9,10
If
effectively
ensure
no
brain,
thereby
preventing
function,
fulfills
requirements
respects
rule.
Ensuring
ceased
permanently
will
not
restarted
allows
donors
based
despite
restoration
abdomen
thorax.
DEATH
DETERMINATION
IN
DONATION
AFTER
CIRCULATORY
OF
Under
current
protocols,
declaration
determining
potential
donor's
permanently.
Three
establish
circulation:
(1)
completely,
evidenced
intra-arterial
pressure
monitoring,
electrocardiography,
echocardiography;
(2)
persists
beyond
time
interval
during
which
autoresuscitation
been
reported
occur;
(3)
intervention
made
restore
declared.11
these
met,
permanence
fulfilled,
validly
dead,
subsequent
donated
does
violate
rule.11
Although
standards
differ
among
jurisdictions,
physicians
who
follow
confident
they
acting
accordance
around
world
have
long
equated
circulation.8
minimum
5
min
absent
establishes
heart
restart
spontaneously
permanent.
standard
was
recommended
Medicine2
common
most
European
countries.12
5-min
confirmed
large
prospective
observational
study
autoresuscitation,
determined
WLST,
longest
between
asystole
4
24
s.13
THE
UNIFIED
BRAIN-BASED
There
widespread
basis
functions,
defined
loss
capacity
consciousness,
breathe,
stem
reflexes.1,14
caused
primary
pathology,
such
traumatic
head
injury,
stroke,
meningitis,
hypoxic–ischemic
damage
secondary
arrest.
provides
when
function
results
arrest,
applying
DCDD,
initially
causes
cease.
Permanent
perfusion,
that,
leads
functions.9,10
Physiologic
studies
dying
WLST
show
activity
closely
correlates
electroencephalogram
becomes
isoelectric
within
30
s
cardiac
arrest
brain15
occur
even
sooner
followed
severe
hypotension
hypoxemia
before
arrest.16,17
Cessation
triggers
physiologic
cascade:
leading
function.
After
complete
circulation,
grounds
and,
therefore,
Permanence
established
elapsed
resuscitative
attempted.
A
ceases
irreversibly
means
cannot
restored.
restored.18
From
inception,
testing
enables
formal
retrospective
assessment
had
previously
(they
restored).
(real
time)
only
According
unifying
death,
valid
because
(see
Figure
1).
true
endpoint
consequence
brain.FIGURE
1.:
dependent
brain.After
permanently,
direct
would
ideal
method
prove
absence.
But
technical
reasons,
electrophysiological
feasible
donor,
particularly
Therefore,
used
surrogate
justified
strict
causal
relationship
exists
ceases:
continue
However,
mere
presence
measurable
necessarily
imply
detected
blood
flow
achieve
necessary
threshold
allow
Yet,
indicates
possible.
These
precise
thresholds
unknown.
GOAL
TA-NRP
IS
TO
RESTORE
CIRCULATION
THORACIC
AND
ABDOMINAL
ORGANS
added
an
preservation
strategy
reperfuse
organs,
reduce
warm
ischemic
damage,
better
assessed
being
recovered
transplantation.
A-NRP,
aorta
clamped
blocked
restrict
whereas
stapling
aortic
arch
vessels.
purpose
vessel
clamping
exclude
initiated,
mechanical
ventilation
restarted.
transplantation
suitability
sinus
rhythm
contractions.
perfuse
opportunity
assess
heart's
functional
do
techniques
succeed
totally
excluding
POTENTIAL
INADEQUACIES
CLAMPING
AORTIC
ARCH
VESSELS
completely
excluded
collateral
arterial
dynamics
autoregulation.
robust
system
arteries
distributed
aorta.
Blood
proceeds
through
carotid
vertebral
ultimately
form
Circle
Willis.
At
level
medulla,
give
off
branches
merge
anterior
spinal
artery.
artery
distributes
cord
supply
derived
cervical
(C1–T3),
(T4–T8),
lumbar
(T9
conus
medullaris)
via
Adamkiewicz.
That
cephalad
toward
along
impaired
major
routes
flow.
Clamping
brain's
main
stimulate
cerebral
autoregulation
generated
NRP.19
Current
data
insufficient
assure
zero
NRP,
although
animal
models
reassuring.20
experiment
small
sample
pigs
found
vessels
prevented
electroencephalogram,
evoked
potentials,
flow,
oxygen
uptake.21
uncertainty
vessels,
Kingdom
Spain
step
severing
distal
clamps
draining
aspirating
ends
severed
while
exposed
atmospheric
pressure.22
maneuver
intended
divert
any
possible
away
brain.
For
restored
other
means.
Animal
performed
reassure
eliminated
incorporated
into
protocols.
could
inform
best
methods
clinical
monitoring
TA-NRP.
To
resolve
over
restoring
studies,
Spain,
should
conducted
TA-NRP,
example,
contrast
angiography.
Given
sufficiently
sensitive
detect
functioning,
areas
difficult
examine,
like
stem,
one
assume
functioning.
RECOMMENDATIONS
DEVELOP
AN
INTERNATIONAL
CONSENSUS
ON
CONCEPT
WHEN
IMPLEMENTED
International
Professional
Societies
Develop
Medical
Standards
Should
Work
Achieve
Consensus
Unified
Brain-based
Concept
applicable
both
distinct.
achieved
brain.23
Determining
outside
context
donation.1
continue.
Establishing
international
professional
consensus
provide
framework
policy
practice,
promoting
public
trust
addressing
barriers
opportunities
Such
accomplished
expert
collaboratives
solid
scientific
evidence.1,14,24
Future
laboratory
research
determine
residual
exceeds
restrictive
vascular
blocking
implemented.
Protocols
Recovery,
Especially
With
Situ
Preservation
Using
Must
Ensure
Absence
Circulation
validated
assurance
stop
experimentally
proven
clinically
effective.
Programs
using
validation
available
consider
implementing
reassurance
continued
TA-NRP–assisted
recovery.25
Surgical
Recovery
Maneuvers
Used
Prevent
During
Be
Legally,
Ethically,
Socially
Acceptable
Discussions
qualified
professionals
families
information
about
aims,
methods,
maneuvers
sufficient
family
members
surrogates
make
informed
decisions
authorizing
donation.
Transparency
conversations
ensures
Some
commentators
emphasized
desirability
pursuing
ex
avoids
ethical
issues
providing
many
benefits.26
this
alternative
associated
substantially
higher
costs
own
limits
countries
where
legislation
observation
period
longer
support
development
practices
communicating
families,
hospital
personnel
explore
their
attitudes
understanding
We
encouraged
efforts
Canadian
panel
adopted
guideline
functions.27
Their
rationale
recommendations
serve
model
worldwide,
Alignment
prevailing
clinical,
remains
necessary.7,8
The American Journal of Bioethics,
Journal Year:
2024,
Volume and Issue:
24(6), P. 27 - 33
Published: June 2, 2024
The
introduction
of
normothermic
regional
perfusion
(NRP)
in
controlled
donation
after
circulatory
determination
death
(cDCDD)
protocols
is
by
some
regarded
as
controversial
and
ethically
troublesome.
One
the
main
concerns
that
opponents
have
about
introducing
NRP
cDCDD
reestablishing
circulation
will
negate
criteria,
potentially
resuscitating
donor.
In
this
article,
I
argue
not
case.
If
we
take
a
closer
look
at
concept
underlying
criterion
for
death,
find
purpose
to
show
whether
organism
whole
has
died.
fulfilled
protocols,
applying
does
or
resuscitate
JAMA,
Journal Year:
2023,
Volume and Issue:
329(24), P. 2123 - 2123
Published: June 2, 2023
This
Viewpoint
examines
an
approach
known
as
normothermic
regional
perfusion,
involving
use
of
ECMO
to
restore
perfusion
internal
organs
in
situ
before
they
are
removed
from
a
deceased
donor.
The American Journal of Bioethics,
Journal Year:
2024,
Volume and Issue:
24(6), P. 34 - 37
Published: June 2, 2024
An
adult
university
hospital
ethics
committee
evaluated
a
proposed
TA-NRP
protocol
in
the
fall
of
2018.
The
raised
ethical
concerns
about
violation
Uniform
Determination
Death
Act
and
prohibition
known
as
Dead
Donor
Rule,
with
potential
resultant
legal
consequences.
additional
concern
was
for
increased
mistrust
by
community
organ
donation
transplantation.
responses
to
these
unable
surmount
boundaries
declined
endorse
procedure.
These
endure.