Everybody. Welcome back to Palm Peeps. We are
back after taking a brief hiatus, a 2
rest and recover after Ats. It was an
awesome conference. But feel like I just got
back on my feet afterwards. Let maybe be
our guests can share our same experience, but
it's awesome to do back with a great
episode. I'm looking forward to. Hey, Monty. How
are you doing? I pay for doing well.
I, I know I feel like I did
a few weeks for the social battery could
recharge. But really excited to be back today,
and I think we're gonna have a fantastic
episode. And today we're gonna be talking about
pre oxygenation methods for endo
intubation, and the pre trial which is hot
off the press in the New England Journal
Medicine, and for the potentially widespread practice changing
results. If you like this is the talk
of the town
amongst Pcc,
I think, Nationally and internationally. And we're so
lucky to be joined by 2 of the
authors of the trial. So first, let's meet
our guests. Yeah. Absolutely. Before Hear, Guys, I'm
just gonna comment, this is the first episode
we're actually recording video as well. This should
be available on Vu yeti and Youtube. If
it's not, it's because we mess something up
and don't hold me to this. But yeah,
if very interested in watching no saga about
this, then you should be able to check
it out there. But now is evidence. So
first, we have Doctor Kevin Gibbs. Kevin is
an associate professor of Medicine at Wake forest
University's full medicine. He... Obtained his Md at
George Wash University school medicine and completed his
residency and fellowship in Pcc at Johns Hopkins.
He's an active researcher in critical care Ari
ards mechanical Ventilation, and pragmatic trial design. Thanks
for coming on the show today, Kevin. Yeah.
I'm delayed to be here today. I'm also
recovering from Ats that I fully recharged That's,
back to a hundred percent. I love it.
Welcome, Kevin. I should've have asked we shouldn't
mask for your autograph at Ats. But just
opportunities for months. But so delighted to next
introduce doctor Jonathan Casey, Jonathan is in the
system professor medicine for the division of allergy,
pulmonary critical Paramedic at Van belt University Medical
Center. He obtained his Md degree from the
University of Louisville school a medicine, who and
completed his residency training in Boston at B
him the women's hospital before going to back
to Van belt for fellowship training.
He's a physician scientist and also has his
master's of science in clinical
investigation. His research focus on comparative effectiveness of
Ic treatments, and he also has a focus
on pragmatic trial
and has support from the Nih and is
after the American Thoracic Society critical care assembly
honored to heavy on today John.
Hey Evening Christine. Thanks for having us. We're
excited to be here, and to talk about
our work, and excited to be the very
first video presentation. If you're watching the video,
then you know why they invited Kevin at
on screen. Yeah. Exactly right We're. We've gotta
go to video now. This is the time.
I... If I had doing that, perhaps, I
would schedule my haircut.
Right.
I love it. So Chose is our standard
disclaimer, As a reminder, this podcast is not
meant for any Specific medical advice that the
views we express today may not reflect those
of our respective employers. And and in cases
that we talk about will be hipaa compliant.
Probably we won't be talking about much patient
level data today.
Great first. So we're gonna get started and
excited to open up the question today with
We're gonna be talking about pre oxygenation techniques
prior to intubation for critically ill patients and
the emergency departments and the intensive of care
units.
And Kevin, I wanna start by defining the
scope and nature of this problem?
And hoping you can tell us why is
this something you interested in researching?
Yeah. So I think Bi will know that
emergency trachea division is really common over 1500000.0
people are debated and emergency department or Icu
with each year in the United States.
Complications from this procedure are also really common
and 20 percent of patients experiencing at,
and 2 percent experienced cardiac arrest.
There there are very few procedures that internal
medicine or pulmonary critical care doctors do, where
you know that in the next 2 minutes.
1 in 50 patients will die. And so
this is a whole really important question and
it's a really big pro.
Yeah. Absolutely. I think that, certainly, as you
get experienced these, mh, our procedures that are
done commonly and people can do them confidently,
but it's... Probably the most anxiety provoking procedure
that we do, just given the a nat
nature and severity of the illness so a
huge topic important to for us to have
the optimal strategy.
So in this trial, you as we're investigating
you exactly that at the optimal strategy for
pre oxygenation to try to avoid that par
intubation hypo
and then the most more severe consequences like
a cardiac arrest.
In general, I think fractionation was a super
fun topic that comes up with intubation. I
like to talk about it with have medical
students in a residents about how much if
you reaction, you don't need to breathe. So
we're paralyzing these patients, but So I last
them. What's the longest someone can hold their
breath. And I think the world record now
is something around 23 minutes if they allow
pre issue and you just... If you can
do a hundred percent oxygen each and our
bodies are very good at this and being
able to have quite a big reserve without
breathing.
However, obviously, our patients in the Are not
competitive divers who can hold their breath for
23 minutes, and we have a a much
smaller narrower window. So, John, before we go
ahead and show where you guys invested could
you discuss the various methods of pre fractionation
that have existed before this, they're posing cons
and which we're are commonly used in the
Ed.
Yeah. I a great question. So the most
commonly used methods of pre action are face
mask oxygen of which there are several subtype
type, so there's a knob breather mask. Or
a bag mass device.
And those of the most commonly used methods
of fractionation. Those are used in about 70
percent of patients in global regis registry I
think that coming out of the operating room
where you're right where it's very easy to
pre patients, those have been considered by many
people to be sufficient. However, as we know
many of our patient or hypo hypoxia even
on those devices and as soon as they
become apt, they rapidly develop hypo.
But there's been a an interest in using
word advanced methods of preoccupation like non eva
ventilation that's still only used in about 15
percent of patients globally, and many of those
patients are not used just for the 3
minute fractionation device, but it had been on
that device, if for support leading up to
the point of intubation.
The pros and cons of each device, as
something like a non breather is really easy
to set up. It takes very little technical
know how to to place an on a
breather, and there's no risk of, any complications
like aspiration.
But a, non invasive ventilation has other potential
advantages. So it it provides... It guarantees a
hundred percent oxygen and, prevents any and trained
error. It provides positive pressure, which can recruit
lung, and it also can provide ventilation when
a patient's acting. Now the potential downside of
non invasive ventilation is this hypo
risk of gastric insulation and aspiration, and I
think that historically that's been 1 of the
reason people. 1 of the reasons people have
been reluctant to use it as.
Thanks so much, John for walking us through
that. And first just going back to your
comment about how long you can kinda hold
the breath. I feel like 1 of our
Ic teams had a a friendly spirited
competition with that. I it wasn't 23 minutes.
I think maybe the the winner wasn't entered,
and it was around 5 minutes. But I
anticipate this may be, a theme going forward.
Yeah. It's 7 impressive 5 minutes. I can
do that. Even with docs.
Oh, Done, that was really helpful If you're
about the the pre oxygenation method that we
have available. And turning a little bit toward
the trial itself. So we previously had some
of your colleagues not sem as well as
Todd and Eddie from the Icu Ed in
Podcast.
So we have discussed pragmatic trial design on
prior episodes. And we definitely encourage. I was
listening today if we haven't listened, definitely checked
those out.
John, but wondering maybe you could tell us
a little bit more about what patients were
included in this study
as well as any, like, inclusion exclusion gray
period and the outcomes and safety points that
you would looked at.
Yeah. Great. Maybe I'll start with the eligibility
criteria and, like Kevin take any any outcomes,
but the eligibility criteria or intended to be
broad. So we're trying in these pragmatic trials
to enroll a maximally general
population. So we try to minimize an exclusion
criteria
to those that are really framed around safety.
So or federal regulations. So have every patient
undergoing oral trachea intubation with
Intubation in an Edi Icu participating in the
trial was eligible to everybody. The only people
who were excluded were those who were children,
known to be pregnant or prisoners,
patients who are apt and required immediate
ventilation in the pre action period
or patients for whom the clinicians felt that
either a non or read or non invasive
ventilation was required or contra.
Thanks, John. And then before we move and
talk about the specifics of the methods could
either of to Kevin and just tell us
about as you were designing it, the primary
outcomes you came up with. And then some
of the cool secondary exploratory outcomes where you're
looking at different levels of hypo of just
set the framework for everywhere. I can certainly
talk about the primary outcome and I'll. I'll
let John take the secondary explored trade once.
The primary outcome for this trial what was
hypo hypoxia See is defined as oxygen saturation
of less than 85 percent. We chose that
value for a number of specific reasons. See
First is that's on the steep port, part
of the option this dis association curve. So
patients with the saturation of 85 are very
steep bun lipid saturation. Curve and are gonna
rapidly them saturated further.
Additionally, that's a value that has been associated
with worse outcomes for patients that are going
to intubation.
Finally, from procedural standpoint to that's roughly
the recommended point where,
intubation attempts are aborted and re is initiated.
From an outcome design standpoint, we had a
real choice whether a binary outcome, which is
to the person to saturated yes or no,
or continuous variable outcome of what was the
lowest option saturation. And I I think we
ended up making the right choice of going
with the binary
outcome. It really tells the story more clearly.
We actually included lowest
saturation as the secondary outcome,
moves in the same direction as the primary,
but I think the mess is stronger with
the binary outcome. John's right than you wanna
add.
Yeah. Kelly mentioned this was... This is a
very trial wonky case discussion, but people listen
to this podcast or probably interested those kinds
of decisions. And
if people have followed our work, the prevent
trial, which is also... Relevant. Here we might
talk about later. Was a trial where the
primary outcome was lowest oxygen saturation is continuous
hear what was the absolute lowest oxygen saturation.
To I think we learned a lot of
things both in the analysis of that trial
and in the reception, it received. What of
what she is that, we... In that trial
looked at both. Lowest option saturation is continuous
and a binary variable, and people weren't as
impressed by the continuous variable. So you can
imagine that most people don't saturate,
and that when you're looking at a device,
it might change the the median action saturation
for all patients from 99 to 96, or
it might prevent extreme cases or hopefully it
does both.
But although the continuous outcome might be more
statistically powerful
If you change the median action saturation from
96 percent to 90 99 percent, that alone
is not very impressive or persuasive to people.
So although you might be sacrificing
statistical power going to a binary variable, that's
the variable that we clearly receive feedback was,
relevant to clinicians was preventing this d icon
outcome that they are worried about their patients
and that's more clinically relevant.
Now, you've decided to go binary your outcome,
you have to decide what threshold to choose.
So there's never been a pre specified
threshold
that defines hypo,
We can look at... Oxygen dis association curves
to say, when does the risk start? And
that's where we look to to pick the
85 percent in this trial, But it's clearly
true that there are many times like Bro
h when our patients have moment maturity saturation
and recover without any ill effects.
I think our thought in this is some
patients.
Unfortunately, when they have low oxygen saturation, don't
tolerate that and have cardiac arrest, but what
threshold? Should you choose for that to prevent
to... As the important threshold to prevent? So
we chose 85 percent as the primary outcome
and then as you mentioned, look, that other
more severe thresholds has secondary exploratory outcome like
oxygen saturation less than 80 percent and less
than 70 percent. That
Yeah. It's really interesting conversation. And I also
feel like the... Having the binary, at least
for me as a reader on it. I
mean, this is already It's a pragmatic trial,
so it's... A super applicable to, you know,
our broad practice and having that binary is
almost feels more applicable too because if you're
they are in innovating and you have your
little Qrs volume and it starts to go
down. It's not like I'm not worried at
85 and I worry at 82. Like I
really worry about the fact that we're having
that downtrend. And so in in some way
as a reader of it, it makes it
very applicable to say, oh, these are the
number of patients we're having it. In lymph
a trial like this, obviously, the specifics of
what you guys did in your intervention can
very much inform what the ongoing side practices.
Kevin, I was hoping you could tell us
in more detail what both p did nation
methods were in each arm of the trial.
Yes. We had 2 groups. We had a
non invasive group in an auction mask group.
In both groups, we recommended a minimum of
3 minutes of pre.
Now if the patient's condition warrant more media
intubation, the operators could.
But our goal is provide at least 3
minutes per issue.
In the non invasive group, we recommended where
we required a minimum
extra pressure of 05:10 water, but a minimum
inventory pressure of Ken centimeters water and a
set respiratory rate of 10 breast per, as
well as delivering 100
percent auction during the fractionation period.
We encouraged clinicians to keep the non invasive
ventilator on after induction of anesthesia until initiation
wearing gossip.
In the auction mask group,
clinicians could use either a non or reader
or bag mask device without positive pressure ventilation
during pre oxygenation.
We recommended the maximum lower rate possible, but
we encourage people to give that least stick
loot per minute, and we encourage continuation of
auction between induction and initiate your.
In both groups,
clinicians could keep on nasal cannula of all
forms including standard board companion as well as
heat hypo blockage cannula.
That's great. And on a very
specific logistical
standpoint, I'm curious how often if you guys
know in the trial or in your own
practice from being part of the trial that
the non invasive device you... Using was the
same device that then became the ventilator or
if you guys had 2 devices in the
room, which obviously
compose some logistical hurdles while you're doing this.
So in the Ico. That's a great question.
The our hope during the implementation phase is
that people will use this with the equipment
that's already available in the room, In the
trial, we gave sight the option to do
either 1 and about a third of patients
were activated at a site that used the
invade the ventilator about 2 thirds.
At sites that use the dedicated bypass machine.
So, obviously, physiological, those 2 devices are equivalent
Just how you wanna train your providers
And I think the idea that people are
gonna bring an dedicated a machine for 3
minutes is even for a intervention that's pretty
beneficial is probably too big ass. So certainly
here the way we're training our staff and
the way that we're asking all the network
sites to train their staff during implementation phase.
Is to make sure they have the equipment
and training if to use the same ventilator
that's already in the rib. We have the
portion experience that re underwent the
recall
right? When we were starting with trial. So
when we were launching of a trial, we
had no dedicated by pet machines, would clearly
the mechanical nightmares.
Out, and that was actually quite helpful for
changing institutional culture. So for the first 2
thirds of the trial we exclusively use. E
and then mechanical ball or pre fractionation. And
I think it's the right answer. It it's
most cost effective and it's very convenient.
Yeah. Absolutely. Yeah. I think that it just
would help... If that's the training, then nobody
is like, oh, I don't wanna go get
this other device and it just makes the
hurdle so much lower. Oh, thanks for... Elaborated
on that. And what we did at our
site, and what I hope other sites do
is, some ventilators,
some hospital stock ventilators that can always do
this. Our hospital stocks 2 types of ventilators,
1 that has an ana modem and 1
that doesn't. So we would preferential have 1
ventilator ready for action so that could provide
non have a mask just hanging on them,
and that's the next 1 they pull when
they're patient, they... And they pre auction it
using that device, and then, use that vice
for invasive mechanical
later and then always make sure that there's
1 in the equipment room setup for the
next patient to be.
That's great.
And...
Have another quick question as I'm thinking about
this. I know John and Kevin you're at
different institutions. Right? And I think that with
this trial, different institutional practices that... Some of
the team members who help with the
Endo
intubation may have been a bit surprised. Great
you usually just reached for the the am
bag and bad mask valve and some people
maybe have walked in and be like what's
going on? But how many others
perceive this and were there any
unexpected
reactions that your head.
So at least locally and I think in
most,
respiratory therapist search. Key partners in these intubation
procedure. I I rely very heavily on them.
I think most people doing so. They're are
the people who are responsible for setting up
the trachea tube. Yeah. They they provide the
back mask ventilation in my institution. It was
really important to get respiratory therapy buying in
at the start. Yeah I think we mostly
jeep bet. I do think that the rest
therapist were appropriately skeptical about a relatively novel
of intervention for them. So all practice was
not to pre actually with non invasive prior
to this study. So we had very limited
experience with that. I think once they got...
Familiar with it and now that they seen
the outcomes, they're on onboard. It just... They
had the appropriate skepticism that of about shame
and their practice
And I think they're right in having that.
And I'll say it's it's all about expectations.
So I think our site was also a
site that didn't routinely do this. We have
a lot of patients who are already on
bi and would remain on bi path for
pre fractionation. There are sites that were already
routinely doing this and that certainly particularly common
at international site like France and Australia that
really routinely do this using the same ventilator
that they'll use for invasive capital ventilation. It's
And once we explain that to our Rt
ortiz and really educate them on why we
wanna do this trial and why this might
be worthwhile. They bought in, so my experience
in our Icu is, Walk in the room
thinking I would require a lot of instruction
or help, and it was already going. The
fellow had already enrolled the patient and the
Rt had already set up the mask was
already correction on on eva before I walked
in the room, and I hope that other
sites similarly find that if you incorporate this
into your usual practice,
that there are a lot... There are a
lot of things during the individual setup that
require more time and energy than does placing
a patient on invasive ventilation, and it was
very easy to do that for 3 minutes
during the setup for other park the procedure.
Such a great point. Well thank he for
sharing your perspective on that. And so you
said pragmatic trial design enrolling,
adults 18 years old and older, But wanted
to hear Kevin from you a little bit
more about... The group of patients that ended
up being recruited as well as the randomization.
Is there anything you wanna highlight about the
cohorts or the intubation procedures itself?
Yeah. I think what... I wanna just talk
briefly about the background. So all prior trials
in this space were limited to the Icu.
At only patients with a acute hypoxia and
respiratory go. They were small trials and they
were not def definitive.
What P did was we enrolled in both
emergency departments and Icu.
And as John alluded to... We had very
broad eligibility criteria here. So we were enrolling
any patient who critical and need to be
today not just with the Q
failure.
The cohorts turned up to be very sick.
Roughly 70 percent were in the Ic icu
with time of intubation, A quarter were on
High key prior intubation, a quarter were on
vas at the time of intubation. The most
common medical condition active during intubation was altered
male. Sense. But the groups were similar, just
very ill, very rod creek populations.
1 part of the question, you might be
asking is this population representative of, who we
anticipate and did they exclude high risk respiration?
I think that's always something about as you
look at the concert diagram. Kevin correct can
correct me on the number, but something like
20 percent of discrete patients were excluded for
urgency of intubation,
And that's not... I think this something that
takes time to set up, We worry how
what proportion patients will be excluded for urgency?
And is there gonna be a large group
of patients that You can't deliver this intervention
in. And thankfully, we found that no the
mass majority of patients, even
emergent intubation, they could place the non invasive
machine And that exclusion rates not dissimilar to
the exclusion rate we've seen in other interventions
that take no time to set up like
our recently completed device trial, video versus direct
endoscopy,
you wouldn't expect a lot of patients to
be excluded for urgency in that trial because
it takes some time to get trial material
to begin an envelope to find someone to
record, even for a A device that doesn't
require a set of time, you guys still
be excluded from the trial because the trial
procedures require time, and the proportion patients excluded
device was not that somewhere from in pre.
So it wasn't that the intervention took so
much time to set up that we were
missing emergent innovation, which had been a concern
of ours going in. And I think thankfully
didn't occur. I think another question is, did
we exclude people who were at high risk
of the safety outcome. So there were people
who were excluded for active Ms assist for
hem, and I think if people are actively
vomiting, you really shouldn't replace him mask on
them. But the trial did enroll really peep
large group people who are at high risk
for aspiration, a lot of people with the
active upper Gi bleeding, people who had recently
taken,
oral intake, So I think this trial, we
believe enrolled the populations that we wanted to,
which it is that people who were really
sick, people who needed be integrated emergent and
the people who were at risk for aspiration.
Yeah. That's great. And thank you for pointing
all those things out. Right? Because to your
point is makes sense that if someone is
actively having E opt you can't put a
mask on them, but it doesn't mean that
the patients you are used doing this in.
We're not high risk for aspiration based on
all the other risk that we know a
c into innovation. Now that we have a
good sense of what the trial was and
who the patients who ended up in the
trial are, John, can we walk us through
what you guys found?
Yeah. Happy to. So as a reminder, the
primary outcome was,
incidence of hypo
identifies an oxygen saturation less than e 5
percent between induction anesthesia in 2 minutes after
intubation, and then occurred at 18.5
percent of patients in the oxygen mass group
of 118
patients.
And by comparison, it it occurred in 57
patients, 9 quite 1 percent. So an absolute
risk reduction of 9.4
percent.
And a p value of less than 0
point 001
and a relative risk reduction up greater than
50 percent.
Yeah. Pretty convincing and clear that we have,
a reduction in the incidents that we're gonna
have of hypo
overall during this. And and I was hoping
you could go a little bit more too
into some of the severe hypo
cardiac arrest, mostly because I think that... We
know that having hypo during intubation is a
risk factor for all these unto untold downstream
outcomes. That being said, I think when you're
reading this, what care about is how the
patient did after the procedure and came through.
And I'm curious what kind of signals you
saw in those outcomes. Yeah. So as we've
already talked about, this threshold of 85 percent,
is somewhat arbitrary, so we have ph reasons
for choosing
recognize that you could told showed another thresholds.
So we looked at other thresholds like as
Oxygen saturation less than 80 percent and less
than 70 percent, and we found basically the
same signal every threshold. So at every threshold
of high
We reduced
by more than half. And for example, the
most severe cases oxygen saturation less than 70
percent occurred in 5.7
percent of patients, in the action mass group
and 2.4
percent in the non invasive ventilation group. And
as you're alluding to, that the question is,
does that matter for patients?
So this has been an outcome that's been
used in many prior trait intubation trials and
that chosen as an outcome because it's closely
linked in observational studies with
the most worrisome outcome
trach intubation cardiac arrest,
but that doesn't prove
preventing hyper will also prevent cardiac arrest. Maybe
it's just that really sick patients experience hypo
and the same patient experience cardiac arrest for
other reasons.
But I thought... In our prior trials,
We've been reluctant to choose Cardiac arrest as
an outcome because even though it occurs up
to 3 percent of patients, it would require
an extremely large trial tens of thousands of
patients to be powered for that rare outcome.
What we were pleasantly surprised to find in
this trial is that by preventing hypo
It appeared that we also prevented Cardiac arrest.
The cardiac arrest occurred in 7 patients in
the face mask oxygen group
compared to 1 patient in the non invasive
ventilation group, a difference that was significant with
a p value of point 04I
think that there's a couple of things. 1
is it proves the importance of this outcome.
But I think this is the first trial
that now really shows that hypo
is an important surrogate outcome during trait on
the patient. And if you prevent hypo,
you should prevent cardiac arrest and save lives.
And further for this specific intervention, it shows
that non invasive ventilation really has significant benefit,
but not only does it prevent the outcome
that we use clinicians cara.
Hypo, it prevents an outcome that both clinicians
and patients k a lot about, which is
cardiac.
Yeah. Definitely some very compelling evidence
and outcomes there John and just to extend
on 1 of the the outcomes kevin, and
anything that you wanna add about the
aspiration safety, comes in and we talked about
that risk, a few times already during the
show, but wanted to see if you wanted
add think. That's right.
I think I I think a lot what
drives clinicians behavior is about in
seizures fear of aspiration.
We we don't know
what's in patient's stomach at the time often
that they are not fasting
and that really guides stations both during the
fractionation phase and also after induction
that decision whether or not from the liver
positive pressure ventilation.
Really focused the design on trying to capture
aspiration. So we we had a number of
exploratory safety outcomes that we're focused on it.
The first was operator reported aspiration. So I
been the procedure the person doing the airway
wrote down whether they the patient experienced
aspiration during procedure.
Additional safety outcomes were new infiltrate on chest
and imaging after activation,
oxygen saturation in 24 hours, and a fraction
inspired auction at 24 hours.
There was no statistical difference between any of
the groups. Between the groups and any of
those outcomes, suggesting that there was no risk
aspiration. In fact, there are numerically few aspirations
in the knowledge ventilation group and the option
mass group. This is a really important binding
because
I think this should really encourage clinicians to
reevaluate the risk benefit analysis of deposit pressure
and fractionation, positive pressure. After ind
and their decision making.
I would point out that Doctor Casey is
the first author of trial We've looked at
positive pressure ventilation after induction, comparing bag mass
ventilation into canonical rapidly within innovation. And they
also found no
between receipt deposit pressure
ventilation and aspiration.
Yeah. So for me, my takeaway is that
Non invasive ventilation deposit pressure ventilation does not
appear to be a substantial risk for aspiration
during intubation.
If the risk is there, it's very small
answer literally outweighed by the benefits of preventing
ty.
And I think if I may, I'll just
jump in and say that. I think 1
question, this is a very strong held view
by clinicians. So how do we get to
the strong held view the positive pressure ventilation
isn't safe after you,
given a neuromuscular blocker and, it's been 1
of the fun parts of research like this
to dig into the data and say, where
did that come from? And the answer is
that the concern was raised in the 19
fifties when we started doing trait home division
for the first time.
And the data that they gathered at that
time was pretty poor, but they took healthy
volunteers to the operating room and paralyzed them
and said, how hard do we have to
squeeze the bag before we can hear air
on their stomach?
And the answer wasn't even some of those
studies that suggested that it never or rarely
occur and some of those studies they establish
threshold that it could occur... Might occur in
normal banking, and that led to people saying,
we we shouldn't do this. Those are pretty
poor surrogate for what's happening in clinical care.
And I think the other a
relationship that has maybe
convince people
is that when do we bag people. So
if we don't bag them prop.
Only bag them when things are going poorly?
And so what is it about, intubation where
things are going poorly that leads to increased
race rates of aspiration? Is it actually bag
or is it the fact that we still
have a learning scope and their throat at
5 minutes when the s station might wearing
off? I think people have these
relationships that are perhaps not based very strong
science.
We now have 4 trials as Kevin mentioned,
our prior prevent trial the cr trial and
the 2 prior small trials and non the
ventilation that Kevin mentioned from France that were
conducted by By lord and group That and
all 4 of those trials have looked at
causing pressure ventilation after induction and have looked
at aspiration as a primary safety outcome and
none of those trial has there been any
signal for increased activation. But I think that
should be pre reassuring that
during
t intubation, a short period of approach fl
positive pressure of ventilation at normal pressures
doesn't increase the risk of aspiration, or even
if it does, you could say these are
rare events and altogether these trials have only
enrolled several thousand patient. If there is any
difference, very small,
and the rate of that difference, it is
dramatically smaller than the benefit from pipe... From
hypo. Yeah. But I hope this trial and
the body of evidence that building makes people
really reevaluate those
traditionally held beliefs.
Yeah. And I wonder if the fact that
you had some... The patients that you mentioned
that were excluded just tells people that, yeah,
You can, basically, based on your best clinical
judgment,
put yourself in this wrist. That's very low.
You're basically excluding these extremely high risk patients,
and these were just based on
clinicians bedside clinical judgment. And so once you've
taken them out, then you can feel really
confident that you're not gonna have aspiration even
though that there's this theoretical risk. Yeah. Can
Push back a little bit on that? Please?
Sure when we don't. Maybe we should cleared
them. Next time me, there's so no aspiration
or with joss, if Was was right. That
someone who is vomit in their mouth should
not be placed where Gonna be
but I just don't think clinicians are that
good at predicting outcomes. And so,
I don't think we included
high risk patients
in a inappropriate or I don't think we
were so good at at assessing risk for
aspiration that we were able to identify those
we're at high risk and exclude them. Or
if we were, be the only condition work
clinicians are that trick. And certainly, I'm not
that.
I just think that this is probably
not a ph physiological.
Relationship between positive pressure after induction as.
K Kevin sensitive to that because the... This
was the what the takeaway from the event
trials but we similar findings the prevent trial,
and if you go to update up to
date today,
they recommend that you should only back people
who are high risk of the outcome and
low risk for aspiration. And I disagree with
that. That's not the way we did the
trial. We tried to include everybody, and we
allow always want to allow clinicians do with
everything is right for their patients. And we
agree that you shouldn't put a mask on
people who are actively vomiting, and there may
be some clinicians who participate in the trial
who excluded people who are iris risk
many clinicians include all other patients who weren't
actively vomiting. Like myself, I didn't exclude a
single patient for,
risk of aspiration And those patients are well
represented in this trial, and there's no evidence
that there's any increased risk. But I think
clinicians should
think about how they operationalize this. I agree
that a patient who's actively vomiting, maybe even
1 who tick a, and looks shady. You
might think about not place this mask on.
But I think the vast majority of patients
should be begin this intervention, and it's not
as if you should be assessing risk factors
for aspiration and then excluding patients from this
intervention. That's not the way we did the
trial, and that's not the the population I
think this should apply to. That's great. Thank
you for pointing. No. I appreciate the shooting
feedback on. I think that's super helpful. Think
about because when you're reading it, and then
you're gonna take it to your bedside, then
you can feel more confident. I love that.
I I do have 1 more question too.
And it's very... This made me a a
difficult question
about the data to analyze through the data.
But I'm curious. I know that you guys
have also done prior trials on first pass
success and you need video versus direct lara.
I'm curious if not that there was a
difference between the 2 groups. I know from
your supplement that they had good first pass
success in both groups. If the patients who
had hypo,
especially that severe hypo
had longer durations or more times or they
didn't have first fast success I'm just thinking
about my own experience, like, when that patient
starts getting hypo.
That's when everyone starts getting nervous. And that's
when things kinda start getting a little more
chaotic during the intubation procedure, and I'm curious
if you guys saw any signal like that.
So it's definitely true that when you fail
on your first attempt, you at increased risk
for all kinds of bad outcomes, including hypo.
And so, and intervention like this might be
more protective against cases like that. Challenge is,
you don't know going in who you're gonna
fail in. So that's what we call a
post randomization variable. So we tend not to
look at a lot of analysis like that.
Because you should make decisions how you treat
patients based on what's noble the time you
have to make that decision, and I don't
know when I'm on creation device if I'm
gonna fail or not. By bet. I better
do the thing that gives me the best
chance whether or not I feel. So that's
1 answer. The second is that we do
look at this and say, are these outcomes
occurring only in patients who had failure in
the first attempt or not. And the answer
is even though when you fail on the
first attempt you have a higher risk of
hypo,
That's the minority of patients we succeed in
the first attempt in 85 percent of patients.
So most events of hypo are occurring in
people who We successfully activate in the first
town. So we did everything right with everything
perfectly well. We had a short and successful
debate and the patients still experience ty senior.
And so those patients also benefit. But he
this also comes up when you talk about
operator experience. But this intervention may be even
more beneficial for an periods operator who's like
that it take longer to debate and expose
their patient to a longer period of apnea,
But it's also beneficial for already experienced operators
who are likely to... Your patient in the
first attempt.
Yeah. It's so great. Night. I just was
just thinking, I was like, there is not
a little bit of pushback from Kevin Gibbs.
Is is it really Kevin's. Thank you and
just I think having us think of different
perspectives.
I think 1 other question of Fe and
I were also just thinking about chew was
disease of hypo cannula for pre oxygenation. It
looks like there were some, people on hypo
cannula prior to the intubation and then underwent
intubation per a trial protocol
we're both wondering if if you wanna share
any thoughts of incorporating hypoglycemia nasal cannula
and to trial methods in the future or
anything that you wanna share about that?
Yeah. I think consideration of pap leukemia is
really important for text.
First comment I had is that p does
not inform the use of hypo
for fractionation. It it was allowed in both
groups.
It occurred more commonly in the auction mask
a non invasive group. Though, we specifically didn't
analyzed whether that impact the rates eye
study.
On a personal level,
I'm a little skeptical about using hypo cannula
as a fractionation strategy. This has been studied,
and the data is quite mixed. In some
studies it's equivalent to non invasive in subsidies.
It's not. And says some studies is not
better than an auction mask.
What what is true is that hypo
is not provide
positive pressure ventilation after induction vantage. And so
all the benefits that you experienced with positive
pressure after production do not are not delivered
by hypo k.
From a practical standpoint,
many ventilators are capable delivering high nasal cable,
but not all, and certainly, no ventilators are
capable of delivering both non invasive ventilation and
on high occasional simultaneously?
So you're really confronted with a choice of
which of these interventions are you going to
use for your pre preoccupied strategy?
From my standpoint, we have robust data that
non invasive ventilation is
superior auction masks
and decreases the risk of cardiac arrest during
Debate. And so that's the strategy that I
would choose. I I don't think it's really
practical to wheel in and the height occasionally
and set that up and then for 3
minutes while you're... While even you could disconnect
the non
layered machine. Not based mask machine and deliver
not a stimulation. But John did additional opinions
on there? Yeah. You could tell. This is
something that we've talked to a lot about
and thought a lot about the design phase
and even in the short time and published
it and asked a lot about. And just
to explain arc our kinda of rationale for
why it wasn't either mandated or it of
the control intervention or included a third arm.
The first is that it's not used very
commonly. So if you look at national
And you look at the data from Our
fire network In the tube study, for example,
which is the best international registry on treatment
intubation practices,
high cannula as patient only use 8 percent
of patient. So not being done very commonly
now, the advantage of P cannula, even over
a device like non invasive ventilation is that
During the time that you're performing trait on
intubation, the in the mouth, you can still
have this high cannula in place, and maybe
be delivering oxygen through diffusion even on the
patient's acne, they'll called ethnic
oxygenation,
That a potential benefit really cite a lot
of people and appears unfortunately to have been
overblown. So now there been a lot of
trials looking at ethnic oxygenation that have shown
no benefit or a small beta.
And trials that have looked at Hypo cannula
compared to face mask as Kevin mentioned have
have not shown a difference, maybe differences in
some subgroups like patients with severe hypo,
but no benefits overall. And then there's AAA
trial that directly compared hypo cannula on non
invasive ventilation, the the P Lead 2 trial
and that I hope to find a benefit
of high cannula and found that not only
was it not better than a non invasive
ventilation actually appeared superior in patients who high
risk. So looking at that body of evidence,
we felt... If you're gonna bring a special
device in the room. And I think it
is important to note that many ventilators can
and deliver either high flow or non invasive,
but not both, as Kevin mentioned. So if
you're gonna bring that device in the room,
You should probably bring in the the... And
you should bring the device that's most likely
to have benefit, and that's why we chose
to compare. Non invasive that the strategy that
had the best preliminary evidence against the strategy
that people were actually using, which is,
non re breeder or bang mask and fight.
I think High cannula is something that I
think people will continue to ask about and
maybe additional evidence will
accrue, but I I personally believe that preliminary
evidence, say just and that there's...
That it's not certainly not better than and
probably not as as not basis.
Thank you, of, Kevin and John for for
walking us through that, and you've already talked
and alluded to several of the main takeaways
from this trial.
And I haven't been... I haven't attended an
Icu since the results have come out. But
just a quick question. I'm just interested for,
I don't know if you have are Kevin
and John. How have how has your day
to day personal practice changed from these results?
For me, I I think the the most
striking thing about trial. Think that I I
was not prepared for
was that non invasive ventilation benefited all subgroups.
And even patients who were not hypo or
who I not classified for being at high
risk for saturation invasion? Had less hypo when
they received non invasive. So patients who on
room air who did not have a diagnosis
of respiratory failure at a lower incidence of
hypo
when they were p with non.
That's really powerful for me. We're we're reducing
the risk of bad outcomes even in patients
who were at low risk for high bias.
And so my practice assistant to adopt, adopt
this broadly.
Essentially any patient I innovating will receive non
invasive pre fractionation.
Yeah. I totally rude Kevin. I think if
you'd asked us in our heart of heart
says investigators what we would find.
I think there was a range of pins
within the group and we actually evaluated that
before we showed the the results. And there
were a fair number within the network who
didn't think it would be beneficial at all.
And there were others who thought, I would
say the majority opinion might have been that
would only be effective amongst those who were
high risk. And I think that's probably where
landon. I thought this was gonna work, but
the benefit was gonna be largely or all
in people who were high risk who were
already line of oxygen were be for respiratory
failure. And we found that the effect was
really consistent across all groups as Kevin mentioned,
even people who are being integrated for ultimate
status, even people who are on room air
with the time you made the decision it,
even amongst those people you cut in half
the risk of I see yet. But I
think that's really changed the way that we
have have approached the implementation of our own
site. As Dave mentioned, it takes effort. So
it we put a lot of effort in
during the trial to make sure we could
deliver this intervention well.
And then the trial ended, and,
we didn't know the results yet, and we
fell out of the habit. Nah.
Now that I'm back on, I asked for
it, and it has not... But I don't
ask it. It doesn't happen, and now we
are intentionally...
And now that the trial results are public
intentionally implementing this in a very systematic way.
So I hope that going forward, every patient
entity in my Icu will receive this, But
it's not gonna happen on own and gonna
happen through word mouth it's gonna take interfacing
with the Rt ortiz and a really intentional
approach to implementing the direction.
That's great great.
John, the only thing that I think that
you meant to say was instead of your
heart of heart, you met your lung of
longs. Right? Is where you're everyone. Felt like
this if you can have. You got I
Chris is an awesome was discussion though so
much for conductor the trial or for the
great work that you're doing, and then for
coming on the show to talk about it.
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