ladies gentlemen my name is Casey column
one of the nurple care physicians at in
the Emory system now over at Midtown
more so but I wanted to talk to you
about post cardiac arrest mannequin and
really I was asked by the other
organizers to talk about a recent trial
called the princess trial which was
presented in Chicago and their most
recent AJ meeting which apparently
garnered a lot of discussion so I was
asked to talk about that and then sort
of frame it a little bit within what we
do currently I have no disclosures and
at the end of this talk like that week
at least
or you could contextualise this
particular trial within the overall data
that we have on post cardiac arrest a
man that management what does it mean
was it be going forward what does it
mean for us at the bedside in terms of
our practice and then to describe the
existing standard that would be at the
end we'll talk about again framing this
but what is the existing standard and
how does this change
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that's your what happen then this
question is where you have the question
again this is where you had the question
no well - but what temperature does your
do you or your institution use or
postcardiac arrest managing just as an
introductory question do you use 32 to
34 do you use 36 do you use a range from
32 to 36 or do you avoid fever but you
don't use target temperature management
so yeah I think this C being 71% that is
in line with the guidelines that exist
which will sort of talk about at the end
I do want to point out that 5% of folks
avoid fever which is a little
problematic depending on how it's done
because we know that fever is is
associated with poor neurologic outcomes
and so if you wait until someone has a
fever and then you treat it you're often
behind the curves and you're incurring
negative outcomes until you get the
fever down back to active fever but will
again talk about that at the end as that
comes up at the end where we go from
here
so we know that the paradigm shift being
occurred back in the early 2000 2002
with the publication of two landmark
papers the Hakka trial on the Barnard
trial which really set forth a standard
of care for cardiac arrest or post
cardiac arrest management in outs that
occurred outside of the hospital these
both demonstrated that 32 to 34 degrees
or 12 to 24 hours led to improved
outcomes less death and it has become
the standard of care and as we sometimes
see after a paradigm shift
there are numerous questions that are
ever that come about because of the new
paradigm new puzzles to solve and we
have seen over the past almost 20 years
that there have been numerous
investigations on what about shockable
versed on shockable rhythms do does one
population benefit from another what
about in hospital cardiac arrests have
been numerous studies on in hospital
cardiac arrest and does in hospital
benefit just like out of hospital does
the duration of hypothermia are target
and temperature management does that
matter it is 12 hours at a low end give
you any benefit versus 24 hours or 28
hours or 48 hours which a recent
publication came out and what about the
different types of cooling devices in
endovascular cooling in which a catheter
is placed in the vessel versus surface
cooling like a great number of us to do
with either partic Sun or Cincinnati
sub-zero sort of blankets have like
all devices and so these are all puzzles
that are being investigated and we know
that one of the biggest puzzles that has
been looked at is the paper that came
out in 2013 that compared 33° as a
target which is sort of the standard of
care versus 36° which some people
mistakenly called normothermia 36 is not
the normal temperature it is hypothermia
it is less hypothermia than 33 and it
must be controlled and we know that the
answer to this was that there seemingly
no difference in terms of outcomes
between 33 and 36 writ large we can talk
and last year I talked to them much more
in depth about some of the details we
don't have time for that this year but
it's an interesting question but
interesting enough if you go to the New
England Journal of Medicine where the
TTM trial is and you look a few weeks
later at the inevitable comments that
come home
there was a editorial that came out that
was written by a fellow named tiered
worker who said wait a second that's
hold on there are a whole bunch of
problems with the 33 to 36 with the DTM
trial for example it took six hours to
get to their target temperature maybe
that's not in line with all the data
they need to do it faster if we got to
target temperature of 33 much faster we
would have much better outcomes
you know don't put the cart before the
horse but think about it was that he was
actually conducting a trial at the time
called the princess trials in which they
were looking at rap
onset of hypothermia and that's what I
was asked to talk about but I wanted to
ask you first what's the biggest barrier
um they should be at the end yeah the
husband's ledger but we couldn't begin
maybe come after this how about that too
much very good look up we'll come back
to this in the energy that should be the
last question so um so we've seen that
when we think about some of these
puzzles we have let's look at the
optimal temperature 33 verses 36 and
then we have this question what about
the time that we we achieve the target
temperature how fast is beneficial and
so that's what the princess trial looked
at in which the aim was to determine the
effect of inter arrests initiation of
target temperature management in the
field so EMS was actually initiating
hypothermia
in the field prior to a standard which
is when they get to the ICU so if you
think about a clinical trial that means
that they have to they have to get to
the patient they have to make sure that
there are no exclusionary factors they
have to enroll the patients and get the
trial in the field while they're also
resuscitate information so that that is
a daunting task and then the goal was to
look at how do patients do in terms of
their and their outcomes and so our
current clinical practice is what I
described patient has an arrest and
we get a return of spontaneous
circulation they get brought to the
emergency departments and then to the
ICU and at some point after they arrive
to the hospital either in the IDI or the
ICU target temperature management is
initiated for a period of time generally
24 and then there's an outcome at some
point the princess trial actually tried
to move the temperature management as I
mentioned much forward into the arrest
setting so a big a big sort of not a
paradigm shift in a sense but certainly
one of the puzzles pieces to be added to
this picture of partying at the rest and
so how they did that
was it they used the novel device called
the Rhino chill and the device is here
and it actually goes into the nose right
here and it sprays this cool mist that
kind of cools down the blood flow around
the brain this flank
sort of the sphenoid area and the brain
deep down kind of cools about the
pituitary's right their target in terms
of management of temperature and so they
don't have to put IVs they're not
putting blanket trawls on people they're
actually just gently shoving a thing up
in someone's nose as they're gonna be
sleeping
and they're turning it on and it's a
very it's a small device I mean it's
almost like us all right very tiny
easily transportable and then can get
folks to and this particular trial we
see that they did not out of hospital
cardiac arrest I had to have a bystander
witnessed arrests happening over 18 EMS
had to respond within 15 minutes to the
call and then they're having the right
return of spontaneous circulation prior
to the initiation of who it's a very
very rapid response and initiation out
in the field and then if they were over
80 the clinical history and the the
trial compared to rapid onset puling
versus the standard of care which is
very similar to what we are generally in
the EDR of an ICU arrived device it's
available 677 patients quite a large
study for example the Barnard trial had
77 patients the hakka trial at 260
patients so large study pretty much
equally randomized they had some
dropouts or the device didn't work and
things of that nature so in general they
pretty good comparison and this is the
time that they reported on average eMS
responded and initiated cpr of the nine
minutes it has airway in the field
within 14 minutes they had randomization
into the trial within 17 minutes and
they cool they started cooling within 19
minutes so think about our practices in
the hospital how often do I even get
cooling started within 19 minutes of a
patient arriving to our ICU and it's
amazing so how it standing there what
they found in general just so folks know
that there was really no difference
between the two groups in the
development of cardiac arrhythmias in
the hospital you know sometimes that can
be seen afterwards there's no difference
in the development of cardiogenic shock
they were pretty equal between both
groups no differences in the development
of pulmonary edema and no differences in
the requirement or need for pay
suppressors they were all equal across
the rusical
and we can see in this graph here a
clear difference between the control
group which is the standard of care in
red and the very rapid onset of cooling
in the intervention and they may have a
time to target 101 minutes versus 182
and so they buy to almost an hour sooner
ultimately in getting those patients now
if we look at the data
their primary outcome us Sarah no
performance scale at 90 days and one of
those this is is those who survived do
they have no disability whatsoever
they're normal that's a CPC one or do
they have very mild disability mild to
moderate disability where they may need
to go to outpatient rehab but otherwise
they do well there isn't a non
and if you look into this intervention
in the standard of care group 13.5
percent of people had the primary
outcome have very good out of CBC one or
two whereas the intervention group at 16
and point six okay so there's a little
bit of a difference
that's a non statistical winners but if
you break it down by rhythm because they
took all comers regardless of the type
of rhythm or was a chocolate or dark
chocolate they found that there was a
signal in the v-fib that had an initial
chocolatey people where in that group
there was again a difference
thirty-four percent in the early cooling
in almost 35 verses about 26 percent in
the standard of care
now this too was non significant but was
close to significant so all in all these
were some of the celebrated results of
the trial that there's potentially a
signal that we can potentially need to
divide patients out some are responsive
to early initiation of cooling some
appear not to be that makes sense if
someone has a PDA arrest and you don't
figure out why they PE like they may not
and they probably won't recover so
that's something in the field that we
think about a lot they seem to show that
early initiation
in the early the earlier that cooling
was initiated the actual better
association without them so that there
may be a point to initiating early
cooling and that all sounds great until
you take a step back person how does
this compare to the Hakka trial how does
this compare to the Bernard trough how
does this compare to the TTM trial
because those numbers seem really low
and sure enough they they are and well
the next time one will show that so what
we take away from this trial is that we
can do excellent well-designed trials
where we can intervene as close to the
time of cardiac arrest and we can do it
well the trans nasal cooling is safe and
allows for a significantly shortened
time of onset so there's a new device we
can use it's always fun to have the
devices the fear nerve early initiation
does not clearly benefit all patients
without a hospital cardiac arrest but
that there may be a signal in certain
subgroups which we don't really our
South at this moment and so let's
compare it to the traumas so the hakka
trial and the Barnard trials are the are
over here on the left their favorable
neurological outcomes were fifty five
and thirty nine percent and they used
about the same measurements a CBC of one
or two I went back and double-check so
fifty five to thirty one thirty nine
percent CBC one or two in those two
trials so even the non the normal xxx
had thirty nine percent good recovery in
the TTM trial 36 versus a thirty three
trial forty about 45 to 47 percent and
forty four to forty seven percent again
there's no difference between the two
right those are favorable neurologic
outcomes
but in this trial 16 to 13 percent it is
severely severely lower than the
standard of care and even their standard
of care was quite low so what does this
mean nobody really knows at this point
in part because the trial is still
ongoing what was presented were
preliminary results at 90 days and the
paper has not yet come out so if we you
know think about early cooling
especially out of hospital and people
are talking about we need to do this
faster out beyond outside I think we
need to hold off for a second to make
sure we look at all the data from the
trial and to put it into context with
the data we have from previous drugs
because it actually may be unsafe and if
you go to some meta analyses from Italy
they've actually demonstrated you know
not good quality clinical trials like
this but there is this suggestion and
early initiation or some reason is
associated with poor outcomes no one
really knows yet because if you go to
the lab when I worked in the lab on
hypothermia
we started hypothermia immediately and
we had great uploads so why is it
different in humans and it's probably
because humans are different we don't
know yet but this is an example of
something getting a lot of buzz that
maybe we need to take us a step back and
not run too quickly into changing our
standards and so what does this mean
so there seem to be a range of effective
target temperatures not just one 32 to
36 at the time to target temperature may
be effective from 0 to 6 hours 6 hours
were all the other trials generally
achieve their target around
six hours but moving it forward or not
or we can do that safely in duration of
target temperature management appears to
be effective when we stay to sustain it
for at least 12 hours up to 24 a baby
who 48 recent trial showed there's no
difference between 24 48 hours 28 and in
48 hours and there may be subgroups the
benefit from very specific targets such
as v-fib v-tach and so on those trials
haven't been done yet that's where I
think that the future should go but this
does sort of nebulous nastasi flecked
what is suggested in both the a and the
American community and there are
critical care society guidelines as well
as ill core which is the International
Society for survival Committee on
resuscitation and themselves but at age
a okay so where do we need to go from
here subgroup tests biomarkers who
benefits from what and quality measures
which include reducing the variability
and that's kind of what yeah here so
what do you figure you know what is
senior practice the most important
factor for cardiac arrest outcomes in a
visit the duration is it how quickly is
temperature avoiding complications where
we're at now as certainly we're trying
to solve some puzzles
and I think just like this we're trying
to figure out what we want we are trying
to solve some puzzles we don't know the
optimal care there's no reason right now
to deviate from the standard of care
post cardiac arrest but certainly you
know moving rapidly into bringing people
cool you know cold down to 30 to 34
degrees very rapidly may be unsafe at
this point and continuing our standards
of care it's kind of where we're at at
this point and I want to raise up
avoiding complications and you can move
on to the history of that and hear where
we're at now in sort of the care
certainly puzzles are being solved
that's the research project process in
the hospital we have a huge quality
issue in terms of picking targets
sticking to targets moving between
targets I've seen that starting off 36
and then new attending comes on and then
it goes down to 32 and so I think one of
the great areas that we can all work on
as we're doing research is improving our
quality of care that were providing in
the post arrest situation and coming up
with new strategies to actually maximize
overall
thank you
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you