Circulation December 20/27, 2016 Issue

Dr. Carolyn
Lam:              
Welcome to Circulation on the Run, your weekly podcast summary
and backstage pass to the journal and its editors. I'm Dr.
Carolyn Lam, Associate Editor from The National Heart Center and
Duke National University of Singapore. We have such a special
issue today. You see, it's entirely focused on resuscitation and
I am delighted to have with me today, Associate Editor, Dr. Mark
Lane from Puffs Medical Center, who really put this issue
together. Welcome, Mark.


Dr. Mark
Lane:                 
Thank you Carolyn.


Dr. Carolyn
Lam:              
Mark, maybe you could start by telling us why the focus on
resuscitation? I do believe this is the first time we've done
this at Circulation.


Dr. Mark
Lane:                 
Yes, this is the first time we've done this at Circulation. It
really was a confluence of a couple things coming together. Once
is that over the spring and summer, we had a very high volume of
high quality resuscitation papers come to Circ. This was not
something that we actually asked for but we noted that there were
a number of these. Also, it's an important time in resuscitation
because a number of the resuscitation counsels across the world
have called for improvements in the survival rate, noting that we
already have the tools that we need to increase survival and we
have to better apply these tools. The HA has provided a goal of
doubling resuscitation and resuscitation counsels in Europe, New
Zealand and Australia have also echoed that call.


Dr. Carolyn
Lam:              
That's great, so this is a really important issue. I just echo
your words about their being a remarkable number of original
papers. We have seven and they're just such high quality. Let's
chat through them, shall we? I'm going to go by pre-hospital
setting to the out of hospital setting and finally end up in the
in-hospital setting. Shall we do that?


Dr. Mark
Lane:                 
That sounds great.


Dr. Carolyn
Lam:              
The first paper is really about identifying patients at risk for
pre-hospital sudden cardiac death at the early phase of
myocardial infarction. You want to tell us a bit about that one?


Dr. Mark
Lane:                 
This is a study coming from the emergency medical services in the
greater Paris area, where they looked at their cardiac arrest and
STEMIs over the last seven or eight years. What they were
specifically looking at is, can you identify STEMI patients who
are at risk for having a cardiac arrest, because if you could
identify those patients, you'd want to get there very quickly
because if you know they're going to arrest or they're going to
have a cardiac arrest, then having a defibrillator there would be
very important.


                                               
What they found, is that you can actually identify STEMI patients
who are higher likelihood of arrest and those STEMI patients are
those with younger age, they're not obese, they don't have
diabetes. They have shortness of breath in addition to their
chest pain and they have a very short delay from the time of
chest pain to their call EMS. That is they're very concerned
about their chest pain. You could use these characteristics to
predict which STEMI patients, which chest pain patients were at
highly likelihood of having a cardiac arrest. There was as much
as a 19-fold difference between individuals without any of these
factors and individuals with several of these factors.


Dr. Carolyn
Lam:              
What I like about this, is that simplicity of that score. Age,
symptoms and kind of the absence of diabetes, absence of obesity
and that short time frame. It's something that could be asked on
a routine questionnaire by EMS dispatchers, for example.


Dr. Mark
Lane:                 
Right. It highlights the importance of the dispatch system. That
simple questions, you can really stratify risk and it's not just
getting an ambulance out there. Truly stratifying risk in order
to get there quicker.


Dr. Carolyn
Lam:              
There are two papers that deal with out of hospital cardiac
arrest. One of them interestingly focusing on the
neuro-protective effects of Glucagon-Like Peptide-1 analog
Exenatide. Thoughts about that one?


Dr. Mark
Lane:                 
This is a randomized study from Denmark. Notable that there are
very low number of randomized trials in resuscitation so the fact
that they did this is remarkable. What they did, is this
glucagon-like peptide analog is a type II diabetic medicine and
there is some reason to believe that that may protect the brain
after resuscitation and ROSP. They had two goals in this trial.
One was to see if it was feasible to administer a drug within six
hours of a cardiac arrest and the other was to get any sort of
outcome measure of whether this could provide some benefit. They
randomly assigned 120 comatose patients and half of them got the
peptide analog and the other half did not. What they showed, it
is feasible to give IV administration of a drug within six hours
of a cardiac arrest. Unfortunately, the drug they used did not
appear to have any clinical benefit and this was both a composite
end-point of death in neurologic function but also an evaluation
of a brain neuron specific amylase, which was actually brain
damage so they didn't see any biological or clinical
neuro-protective effects of this drug.


Dr. Carolyn
Lam:              
I didn't realize it until you said it, it is very difficult to do
a randomized control trial. This is very significant just for
that. The next study about the out of hospital arrest, really
talks about bystander CPR and I think seeks to answer to what
degree bystander CPR remains positively associated with survival
with increasing time to potential defibrillation. Important
question, what do you think of that?


Dr. Mark
Lane:                 
It's an important question that surprisingly has not been
evaluated that closely. Most either studies either look at
bystander CPR or EMS arrival times but don't look at the
interaction between the two. This study looks at the interaction
between bystander CPR and EMS response time and that's the
critical thing in this paper that's very interesting.


                                               
What they did is, they split bystander CPR with or without and
then EMS response times five minutes, 10 minutes and longer. If
EMS responds within five minutes and you had bystander CPR, the
survival rates with good neurological outcome were 14.5%, which
is really a remarkable number. If there was no bystander CPR and
the EMS arrived within five minutes, it dropped to 6.3%. There
was 2.3-fold higher likelihood of good neurologic survival with
bystander CPR with EMS within five minutes.


                                               
They also looked at the 10 minute response time of EMS and if you
had bystander CPR and EMS arrived within 10 minutes, the survival
rate was 6.7% and without bystander CPR, it was 2.2%. With
bystander CPR and EMS arrival within 10 minutes, there was a
three-fold higher likelihood of survival with bystander CPR. It's
interesting that by 13 minutes, there really was essentially no
difference in those individuals who had bystander CPR or not,
suggesting that at that point it's taken so long for EMS to
arrive, it really doesn't make really much difference between
whether you have bystander CPR.


                                               
A really important paper showing that bystander CPR is critical,
but so is EMS arrival within five minutes especially, but even 10
minutes.


Dr. Carolyn
Lam:              
I like that paper and I really like the way you crystallized the
findings so clearly like that. What I'm also liking is the way,
even though these papers weren't invited or anything, there is
this nice flow because from bystander CPR we now talk about
duration of resuscitation. There's one regarding adults and
followed by one in pediatric population so very nice set of
papers. Could we start by maybe talking about the adult one? The
one looking at the association between duration of resuscitation
and favorable outcomes after out of hospital cardiac arrest from
North America.


Dr. Mark
Lane:                 
The reason that these two papers are important is really the
futility issue. When is it futile to continue a CPR and that's a
very important question. This adult paper is from the ROC
Consortium. The ROC is a North American Seer NIH Sponsored
consortium that's been going on over the last 10 or so years.
What they looked at was outpatients and they had a very large
number of greater than 11,000 subjects and of those 8% survived
with a good outcome. That's 8% of those 11,000. If you looked at
those 8% that survived, 90% of those had return of spontaneous
circulation with 20 minutes. You really wanted to get their blood
pressure back within 20 minutes.


                                               
If you went beyond 20 minutes to the return of spontaneous
circulation, you still could get good outcome. It was less likely
but it was more likely if you had initial shockable rhythm, you
had a witnessed cardiac arrest or you had bystander CPR. If you
had some of those features, then you would argue to continue CPR
for a longer time period. Actually a very nice important paper
that if you had those other three features, you could still get
good neurologic functioning, even with resuscitation attempts up
to 40 minutes.


Dr. Carolyn
Lam:              
Exactly. I thought I saw 47 minutes somewhere, but it gives us a
bit of a guidance when we're making these really tough decisions
and talking about tough decisions and futility, I think it's even
more amplified in the pediatric population, isn't it? This next
paper from Japan talks about the duration of pre-hospital CPR in
the pediatric population. What are your thoughts on that one?


Dr. Mark
Lane:                 
This was a study from Japan, using their nation-wide Japanese
data base. Actually, in many ways mirrored the adult experience.
The number of patients analyzed with roughly the same. This was
nearly 13,000. They looked at 30 day survival both overall and 30
day survival with good neurologic function and 30 day survival
overall were 9% so similar to the 8% in adults and good
neurologic function were 2.5%, which wasn't quite as good as in
the adults and that the duration of CPR also was very important.
Once CPR went out to 42 minutes there was less than 1% chance
that that individual was going to survive with any significant
neurologic outcome. If you had bystander CPR you could increase
that time by four to five minutes but again showing very similar
numbers to the adult population that once you start hitting that
40 to 45 minute time frame, if there's no return of spontaneous
circulation then the odds of survival are really quite low.


                                               
The time frame may be extended a bit by CPR, maybe be extended by
a bit if you had a shockable rhythm. Again, very similar features
to what were found in the adult study.


Dr. Carolyn
Lam:              
What a nice pair of papers. You know, the pediatric paper was
paired by yet another, wasn't it? This one now addresses very
importantly conventional versus compression only CPR in the
pediatric population. Again, from Japan. I know both the
pediatric papers were of great interest because you invited an
editorial on this as well. You want to comment on those?


Dr. Mark
Lane:                 
This issue of compression only CPR versus standard CPR, which
includes compression and ventilation is a very hot one because we
know that if you can do compression only CPR, the individuals
willing to do that type of CPR are much greater than the
individuals willing to do mouth to mouth. In the adult
population, there's been a number of very good retrospective
registries and also randomized trials that showed that
compression only CPR may be very similar ... In fact some studies
better, some studies a little worse than compression-ventilation
CPR.


                                               
Whether this applies to the pediatric population is not clear.
There is more asphyxial arrest in the pediatric population
whereas in the adult it's more cardiac so there is concern that
compression only CPR will not be as good in children. This group
of investigators used the same registry. A little shorter
time-frame. They looked at it for two years and thus only had
2,000 patients in this registry. Of these 2,000 patients 400
received conventional CPR, 700 received compression only CPR and
1,000 did not receive any CPR. The important findings in this
study was that any CPR increases survival so if you did not get
any CPR, your survival was 3.7%. If you got conventional CPR your
survival was 25.9% and if you got compression only CPR your
survival was 9.3%.


                                               
When you compared unadjusted survival with compression only
versus the standard CPR, the odds ratio were 3.42 that standard
CPR was better than compression only CPR. However when you did
multi-variable adjustment, that big difference decreased and was
no longer statistically significant between conventional CPR and
compression only CPR. The same was true when you did propensity
score matching which is an attempt to randomize to match groups.
There was really no difference between conventional CPR and and
compression only CPR.


                                               
From this study, it's clear that any CPR is better than no CPR.
There was a hint here that standard CPR was better than
compression only CPR but because that improvement disappeared
with multi-variable adjustment and propensity score matching both
the authors and the editorialists have called that it's time for
a randomized trial of compression CPR in kids.


Dr. Carolyn
Lam:              
Very nice. That brings us already, to the last original paper.
Into the in-hospital setting and it talks about time to
epinephrine. That's nice. We've got time to balloon and time to
door and and now we've got time to epinephrine. Tell us about
this one.


Dr. Mark
Lane:                 
This was a very nice study from the guidelines database. This is
a data base that the HA is using to evaluate resuscitation in
hospitals. In this database, the investigators looked at times to
the epinephrine administration and then overall patient survival
for the hospitals. What they found is that there was wide
variability in the time to first epinephrine dose. The HA and
other counsels have recommended that it be given as soon as
possible or early-on in resuscitation and in this database 12.7%
of patients had delays greater than five minutes to epinephrine.


                                               
What importantly they showed, when you looked at the hospital's
overall time to epinephrine administration and the hospital's
overall resuscitation survival rates, they were inversely
proportional. That is, the longer that hospitals took to give the
first dose of epinephrine, the lower their survival rate. This
really leads to a very important question, is it the delay in
epinephrine administration that makes the difference between
these good functioning hospitals and poor functioning hospitals,
or is it that the delay to epinephrine administration is really a
surrogate for poor CPR performance. I suspect that both of them
could be true, although I suspect the second one is probably a
higher likelihood.


Dr. Carolyn
Lam:              
Congratulations again on this amazing issue with extremely
important take-home messages just from the original papers. Were
there other papers you wanted to highlight in this issue?


Dr. Mark
Lane:                 
Yeah, there were three research letters and this is a newer type
thing for SERP. These are original manuscripts but in a very
succinct fashion in that they're making a single point. I
actually thought these three research papers were very
interesting also. One was on the mechanical CPR in the cares
database and in this paper they actually showed that mechanical
CPR was associated with poor outcomes in resuscitation so a paper
well worth reading. In another paper from France looked at
pulmonary embolism related to sudden cardiac death and what they
found is that PEs were present in a significant percentage of
people who had sudden cardiac arrest and again if you had a
non-shockable rhythm, female, prior thromboembolism or absence of
heart disease you were more likely to have a pulmonary embolism.


                                               
The final research letter looked at ticagrelor versus clopidogrel
in comatose patients undergoing PCI, a randomized study. Succinct
paper well worth reading. In addition to those three research
letters, there were four frames of reference. These are more a
personal perspective on resuscitation and resuscitation signs
over time and interesting reading, all four of them.


Dr. Carolyn
Lam:              
Mark, that was a beautiful summary and I am sure you've whet the
appetites of all the listeners to just grab hold of this issue.
Thank you so much for joining me today. Thank you listeners for
tuning in and don't forget to tune in next week.