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. And we hope that everybody's enjoyed listening. If you guys are listening now, please make sure you subscribe, give us 5 stars. Wherever everywhere listening and join us back in 2 weeks for
our episode. And this episode was rear edited and produced by myself in Christina Mont, the music's original music by Eric Rogers, and we'll see you next time.