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COVID and ARDS - Back To Basics
5 Plays5 years ago
In this episode of Critical Matters, we discuss the management of COVID induced ARDS.
Our guest is Dr. Eddy Fan, an associate Professor in the Interdepartmental Division of Critical Care Medicine and the Institute of Health Policy, Management and Evaluation at the University of Toronto and a Staff Intensivist at the University Health Network/Mount Sinai Hospital. He is currently the Medical Director of the Extracorporeal Life Support Program at the Toronto General Hospital, and the Director of Critical Care Research at the University Health Network/Mount Sinai Hospital. During our conversation, we discuss phenotypes within ARDS, the best available evidence for the management of ARDS, and other topics.
Additional Resources:
COVID-19-Associated Acute Respiratory Distress Syndrome: Is a Different Approach to Management Warranted?: https://bit.ly/3fMkYOp
American Thoraic Society - Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome: https://bit.ly/2CQTIju
Management of COVID-19 Respiratory Distress: https://bit.ly/2WuwFCw
Previous Episodes of Critical Matters on COVID-19 Induced ARDS/Respiratory Failure:
- https://bit.ly/2OGWF8T
- https://bit.ly/32yO2p7
Books Mentioned in this Episode:
A Portrait of the Artist as a Young Man by James Joyce: https://amzn.to/2OJyiHM
Recommended
Transcript
Podcast Introduction
00:00:06
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:14
Speaker
Sound Critical Care provides comprehensive critical care programs to hospitals across the country.
00:00:20
Speaker
To learn more about our programs and career opportunities, visit www.soundphysicians.com.
00:00:27
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And now your host, Dr. Sergio Zanotti.
COVID-19 and ICU Admissions
00:00:32
Speaker
The COVID-19 pandemic continues to consume our attention with increasing cases around the world.
00:00:37
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In the United States, a sharp increase of cases in multiple states has led to a large number of ICU admissions.
00:00:43
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In previous episodes of the podcast, we've had multiple discussions on the respiratory failure caused by COVID-19.
Managing COVID-induced ARDS
00:00:50
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Today, we will go back to basics and review best available evidence for the management of COVID-induced ARDS.
00:00:57
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Our guest is Dr. Eddie Pham.
00:00:59
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Dr. Fan is an associate professor in the Interdepartmental Division of Critical Care Medicine and the Institute of Health Policy, Management and Evaluation of the University of Toronto, and a staff intensivist at the University Health Network, Mount Sinai Hospital.
00:01:15
Speaker
He is currently the medical director of the Extracorporeal Life Support Program at the Toronto General Hospital, and the director of critical care research at the University Health Network, Mount Sinai Hospital.
Guest Introduction: Dr. Eddie Pham
00:01:26
Speaker
Dr. Fan's research has focused on advanced life support for acute respiratory failure and patient outcomes from critical illness.
00:01:33
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These include investigations on the epidemiology and use of mechanical ventilation and extracorporeal life support in patients with ARDS, as well as on the development of ICU-acquired weakness, early rehabilitation in ICU patients, and long-term outcomes in survivors of critical illness.
00:01:49
Speaker
We are very fortunate to have Dr. Fan today and very honored.
00:01:53
Speaker
Eddie, welcome to Critical Matters.
00:01:56
Speaker
Thanks very much.
00:01:57
Speaker
It's a pleasure to be here.
Research Highlights: ARDS and Critical Illness
00:01:58
Speaker
So I know that you have a passion for ARDS and have been not only part of multiple research trials, but also, I mean, lead author in many viewpoints and in many official statements regarding ARDS.
00:02:12
Speaker
And it seems that for the last six months, we have probably never seen as many ARDS patients in our ICUs.
00:02:19
Speaker
Yes, I think it's the global pandemic has taken hold and unfortunately,
00:02:24
Speaker
Many of these patients have become critically ill and developed COVID-associated ARDS and seeing them in our intensive care units with the ARDS, I think this is unfortunately a pattern that's a bit replicated itself in many jurisdictions around the world.
00:02:39
Speaker
And I think that we were talking prior to starting recording, Nedi, on some of the unique aspects of this pandemic, not only from a medical perspective in terms of the number of patients that
Social Media's Role in COVID-19 Information
00:02:50
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we're seeing.
00:02:50
Speaker
I have never, I cannot recall in my lifetime
00:02:54
Speaker
having whole units of patients with the same diagnosis and seeing one after another being treated with similar therapies.
00:03:01
Speaker
That is something new.
00:03:02
Speaker
But also we were commenting on the angst that this has caused on, obviously, on providers, the stress is caused on hospital systems, but also a very interesting phenomenon related to the dissemination of information or what we call an infodemic and where people seem to be looking for absolute answers, one size fits all.
00:03:22
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And it's a pendulum that swings from one attitude to another.
00:03:25
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And a lot of this propagated through social media, unfortunately, and not through the right channels.
Pandemic Challenges and Global Impact
00:03:32
Speaker
And I think that maybe we could start by just sharing with us what was the motivation for the recent viewpoint you published in Lancet, which I think was what triggered us having this conversation.
00:03:44
Speaker
Yeah, so thanks for that Sergio.
00:03:46
Speaker
In fact, I like the term infodemic.
00:03:47
Speaker
I haven't heard that before, but I'll definitely be using that in the future.
00:03:51
Speaker
But I think that's one of the unique aspects of this pandemic.
00:03:54
Speaker
One is obviously the global reach that unfortunately the pandemic has had in the number of cases that you mentioned.
00:04:00
Speaker
And with that, all the unknowns as this pandemic started in Wuhan and moved its way across the world.
00:04:09
Speaker
And in this age of social media, open access, free medical education, which obviously has many, many pros, some of the cons were, as you described, is that, you know, very quickly you could look to social media, you could look online, and now even traditional media outlets and even, you know, high impact medical journals were very quickly publishing reports of various quality, various
00:04:38
Speaker
methodologic rigor, offering anything from an anecdote to small case series to observational studies, uncontrolled studies, providing opinions on the best management of this pandemic as it accelerated.
00:04:53
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And I think the challenge for clinicians who are already in many cases overwhelmed by the clinical care of these patients and their health systems, as you described, now are being inundated
00:05:05
Speaker
by sometimes conflicting reports of the identification, diagnosis, management, and prognosis of these patients, making it even more difficult in some circumstances to care for these patients.
00:05:16
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So in the usual situation where you think that rapid dissemination of information would be helpful in such a situation, I think that my colleagues and I felt that in many instances,
00:05:27
Speaker
These often unsubstantiated, again, methodologically, maybe not as rigorous information was driving sometimes bad decision making and management of these patients where what we need is careful thought and the ability to learn.
00:05:43
Speaker
from this
Non-specialists and COVID Management
00:05:44
Speaker
pandemic.
00:05:44
Speaker
I think Derek Angus has written a nice editorial about the importance of learning while doing.
00:05:48
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Certainly we need to treat these patients as they become ill, but we need to take a focused approach and a collaborative approach to the management of these patients.
00:05:56
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And in terms of your question about our viewpoint, I think Dan Brody, my friend and colleague from New York Presbyterian Hospital,
00:06:02
Speaker
as the pandemic was hitting New York, was finding that a lot of non-specialists or non-intensivists were treating COVID patients who were surging all over his hospital.
00:06:12
Speaker
And again, in many instances, turning to these non-traditional sources of medical information to help guide management.
00:06:19
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And the two of us wanted to maybe take the opportunity to perhaps collate some of the ideas and some of the challenges that have been going on
00:06:28
Speaker
during COVID in this viewpoint to sort of, as you mentioned at the beginning, bring things back to basics and maybe start to highlight some fundamental starting points for management and obviously individualizing care from there.
00:06:42
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Excellent.
00:06:43
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And I think that that's what we're going to try to do in this conversation.
00:06:46
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And I think it's also important to remember that there seems to be some aspects, Eddie,
00:06:52
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that people are assuming about COVID.
00:06:55
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Like, number one is that everything that we see is highly unique to COVID.
00:07:00
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Whereas, I mean, I think we've never seen this number of patients at the same time, but a lot of things that we're seeing with COVID, we've seen with other infections.
00:07:07
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And at the end of the day, it's not necessarily a unique, unique, unique, different disease, but it's just, I mean, different because we don't have maybe certain treatments, but it behaves, like you said, once it is ARDS or once they have certain things, very similarly to large populations of
00:07:22
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patients with ARDS from other causes as well.
Understanding ARDS Phenotypes
00:07:27
Speaker
Yeah, agreed.
00:07:28
Speaker
I think this is, you know, when we think about other viral pneumonias that lead to lung injury and then the clinical syndrome of ARDS, influenza every year can present also with this heterogeneous picture.
00:07:43
Speaker
In Toronto, we had over 10 years ago, the
00:07:47
Speaker
an experience with SARS, so the original coronavirus infection that led to severe respiratory failure in some patients and unfortunately some of our medical colleagues who treated these patients and also led to respiratory failure that was
00:08:00
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presented as ARDS and then unfortunate complications like multi-organ failure.
00:08:05
Speaker
So I agree with you.
00:08:06
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I think there are obviously, we're starting to uncover some unique aspects of COVID, but certainly there is a component of the lung injury and respiratory failure that COVID induces that is very much like ARDS.
00:08:19
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So I would like to start by talking about phenotypes.
00:08:22
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And I think that maybe we can start, Eddie, with just reminding the audience about the presence of phenotypes in ARDS.
00:08:30
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which is not anything new before we talk about COVID.
00:08:35
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Yeah, I think this is one of the points that we wanted to highlight in the viewpoint, and I know that many people have highlighted both in subsequent commentaries as well as in social media, is that heterogeneity in ARDS has been present since its original definition in 1967.
00:08:51
Speaker
In fact, the group of patients that Ashbaugh and Petty published about in The Lancet
00:08:56
Speaker
were very different and a very different clinical risk factors, presentations, and this sort of thing.
00:09:02
Speaker
So heterogeneity in the syndrome has been present since the beginning.
00:09:06
Speaker
And again, the fact that it is a syndrome and not a disease suggests there's going to be a degree of heterogeneity that you won't see in something like myocardial infarction, which is a disease and not a syndrome.
00:09:17
Speaker
And so I think that's one thing to recognize.
00:09:20
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So we're not surprised that COVID
00:09:23
Speaker
as a risk factor for the development of lung injury in ARDS will lead to a heterogeneous presentation when it occurs and causes people to be critically ill.
00:09:33
Speaker
So I think that's an important thing to recognize, that heterogeneity in ARDS is not a new phenomenon.
00:09:40
Speaker
And I think that one of the things that for me has always been fascinating in ARDS, specifically when we talk about phenotypes, is that in the last several years, after many ARDSnet trials have been completed,
00:09:52
Speaker
re-analysis of these trials looking at latent phase analysis of different phenotypes seems to suggest, which obviously needs to be studied further, that when you take big averages of patients, maybe certain things don't seem to work very well, but when you can classify based on certain characteristics, they might have a better application.
00:10:12
Speaker
And I think that even though that's something that still needs to be studied, I think it's an interesting concept for the future.
00:10:18
Speaker
Could you comment on that, Eddie?
00:10:21
Speaker
Yeah, 100%.
00:10:21
Speaker
And again, I think that's, and maybe here not to dig too deep into the semantics of phenotypes, but I mean, I completely agree.
00:10:29
Speaker
It's the heterogeneity of treatment effect or the heterogeneity in clinical trials, especially when they're large and enroll heterogeneous populations, as the definition allows.
00:10:39
Speaker
And a very good example of that is work that Professor Gannoni has been seminal in is the development of
00:10:46
Speaker
prone positioning for severe ARDS.
00:10:48
Speaker
You might recall that there have been quite a few randomized control trials of prone positioning in patients with ARDS or even back using the older definition, lung injury, acute lung injury and ARDS.
00:11:00
Speaker
And these studies were refined over time that we understood that exactly as you said, Sergio, as we reanalyzed these initial studies and enrolled big populations of patients who have PF ratios less than 300 sort of all comers with lung injury or now what we call ARDS.
00:11:13
Speaker
And we discovered that actually the subgroup that seemed to consistently benefit in these trials was the sickest or the most hypoxemic subgroup and those that underwent proning for a longer duration of time.
00:11:23
Speaker
And so these trials morphed over time, 20 years, to focus more and more narrowly on the sickest patients and on longer duration and proning that culminated in the Proceva study that showed the dramatic benefit of prone positioning in the group of patients with more severe hypoxemia and with longer duration of prone positioning.
00:11:43
Speaker
Excellent.
00:11:44
Speaker
And since you mentioned Dr. Gattinoni, I think that we can maybe move on into phenotypes and COVID.
00:11:50
Speaker
He obviously early on shared some thoughts on possible variations and phenotypes and clinical presentation.
00:11:58
Speaker
And I think that the idea, I think, is very interesting.
00:12:02
Speaker
It's generally a lot of discussion, some controversy, and maybe perhaps, unfortunately, some people jump into conclusions too quickly in terms of what we should or should not do.
00:12:13
Speaker
Could you just share with us a little bit about the concept of phenotypes within COVID?
00:12:19
Speaker
Yeah, I think, again, I think the idea here, and of course, with all respect to Professor Gattinoni, who has taught us so much about ARDS, amongst many other things in critical care, is that there could very well be
00:12:34
Speaker
these important phenotypes or endotypes or sub phenotypes, again, not trying to dig too deep into the nomenclature in COVID associated ARDS, what he's now published a number of times on the L and H phenotypes, which seem to be, again, descriptions of relatively distinct either phases of the lung injury evolution or clinical presentation, whether they're true phenotypes or not.
00:12:59
Speaker
I think that's the part where
00:13:01
Speaker
Again, perhaps a more methodologic lens could be placed on it.
00:13:05
Speaker
One of my colleagues, Carolyn Calfie from the University of California at San Francisco has done elegant work in trying to, with colleagues around the world,
00:13:15
Speaker
to identify some of these phenotypes in ARDS, which are through methods like latent class analysis, a rigorous method of identifying true phenotypes, and most importantly, identifying phenotypes that matter in the sense that if you can identify some differences, that you would treat them differently.
00:13:32
Speaker
And when you treat them differently, that leads to different outcomes.
00:13:35
Speaker
That's the importance of identifying phenotypes.
00:13:37
Speaker
So the fact that
00:13:38
Speaker
Some patients are different than others in ARDS.
00:13:40
Speaker
I mean, this is maybe interesting, but if in the end you treat them all the same and the outcomes are all the same, then identifying those differences may not be so important.
00:13:47
Speaker
phenotypic variation is very important if it leads to differential treatment plans, which lead to different treatment results.
00:13:55
Speaker
So that would be the first thing that I would say.
00:13:56
Speaker
So the identification by Professor Gattinoni of these LNH phenotypes, they seem interesting.
00:14:02
Speaker
Again, I think they need to be corroborated using more rigorous methods in larger data sets.
00:14:08
Speaker
And then most importantly, showing that the management or treatment of LNH phenotypes, if they're true phenotypes,
00:14:16
Speaker
would lead to different outcomes, that would be the other important thing.
Individualized Treatment in ICUs
00:14:21
Speaker
Yeah.
00:14:21
Speaker
And I think an important lesson for myself, at least, was early on, I think, and we'll talk a little bit more about this, I think that people were looking for a kind of like bullets in terms of, okay, everybody should be on high PEEP, everybody should be on low PEEP, everybody should be intubated early, everybody should be intubated late.
00:14:40
Speaker
I mean, and I think that that's what we need to recognize that whether we have phenotypes or not,
00:14:45
Speaker
individual patients need to be treated within the context of their individual situation with the best available evidence.
00:14:52
Speaker
And I think that that is maybe a more important message for the bedside clinicians, which obviously when you get overwhelmed with patients becomes more and more difficult.
00:15:01
Speaker
And it's something that we have to recognize as unique to this pandemic.
00:15:05
Speaker
But why don't we go into just, I mean, talking a little bit about management and start maybe with what you have seen, what you have experienced,
00:15:15
Speaker
and kind of your thoughts on just initially treating patients who present to the hospital with hypoxemia with COVID?
Infection Control in COVID-19 Care
00:15:24
Speaker
Yeah, so I think, you know, I think actually that one of the main drivers, at least at my hospital, and I think it might be, again, different in different jurisdictions, I think one of the main changes in this strategy on managing these patients have been driven by infection control limitations.
00:15:40
Speaker
So in my hospital, for instance, we started off as COVID cases hit here in Toronto,
00:15:46
Speaker
Canada, our infection control procedures were trying to discourage the use of high flow nasal cannula and non-invasive ventilation like BiPAP because of the unclear risk of aerosolization from these modalities.
00:16:02
Speaker
And again, this is a situation where we've had, I would say at the moment, although it seems to be improving, at the start of the pandemic, inconsistent data about the true risk of
00:16:13
Speaker
for healthcare workers in particular, of managing these patients on high flow nasal cannula or non-invasive ventilation and the risk of its aerosol generation and then subsequent infection of healthcare workers.
00:16:25
Speaker
And again, so from our point of view, because we were concerned about, as I'm sure many jurisdictions, about the availability of PPE to protect healthcare workers if these patients were to be managed under full airborne precautions, the availability of negative pressure rooms to put them in, as well as perhaps having HEPA filter in non-airborne rooms, negative pressure rooms, we elected to really sparingly use PPE.
00:16:45
Speaker
high flow nasal cannula and non-invasive ventilation in these patients.
00:16:48
Speaker
Again, not because we didn't think they might be efficacious in the right patients, but mostly because we were concerned about infection risk.
00:16:55
Speaker
Now, as the pandemic has continued and there now is increasing amounts of data, perhaps suggesting that high flow nasal cannula is perhaps not as aerosolizing as we initially believed and perhaps similarly for non-invasive ventilation.
00:17:08
Speaker
We're now cautiously trying to use these, but still under full airborne precautions to protect our healthcare workers.
00:17:15
Speaker
And in terms of extrapolating from ARDS, there's also, I mean, obviously recently published data on high flow nasal cannula in ARDS.
00:17:25
Speaker
Any thoughts, I mean, in terms of what we know from ARDS is just which might be more effective?
00:17:32
Speaker
Yeah, again, I think that's probably a good starting point.
00:17:36
Speaker
Again, we don't have at the moment, although that, again, is changing data specifically in COVID, as much data in specifically in COVID populations.
00:17:43
Speaker
But again, extrapolating from our existing knowledge that, again, in the right patient who isn't profoundly hypoxemic, certainly perhaps maybe best use in those who have hypercapnia, which may not be the most profound presentation of some of these patients who have ARDS, but high flow nasal cannula and non-invasive ventilation certainly have their place.
00:18:02
Speaker
But again, I think as institutional guidelines vary on the trigger point for intubation, certainly traditional
00:18:11
Speaker
thresholds for intubation should still be employed in these patients.
00:18:14
Speaker
So obviously patients who are having decreased level of consciousness, where difficulty protecting their airway or managing secretions, who develop more profound hypoxemia that would require mechanical ventilation.
00:18:27
Speaker
These are patients that should quickly move to ventilatory, invasive ventilatory support as we normally would in non-COVID times.
00:18:34
Speaker
But certainly that there are going to be very good patients who have milder forms of hypoxemia, who are very awake, perhaps some of these also have a component of hypercapnia, who could be well managed in the right monitored setting on high flow nasal cannula or non-invasive ventilation.
00:18:49
Speaker
And I think that an important distinction to make or just to emphasize is that
00:18:57
Speaker
Whether you use it or not, the important thing that I think has been said over and over again is that when you utilize either high-flow nasal cannula or BiPAP, optimize your infection control precautions, but also have a very intense monitoring of these patients because if they're not responding or getting worse, probably delaying things is not in their benefit.
00:19:20
Speaker
Whether they have COVID or not is something that I think we all believe.
00:19:23
Speaker
that we should be very careful with these patients.
00:19:26
Speaker
And I think that's something, a message that sometimes I think gets lost.
00:19:29
Speaker
100%.
00:19:31
Speaker
In fact, I feel that non-invasive ventilation, in fact, is probably in many instances more difficult to implement well and properly than invasive mechanical ventilation.
00:19:44
Speaker
One of the things exactly, Sergio, I couldn't agree more, is that these are not, especially in COVID times, a fire and forget situation.
00:19:51
Speaker
These patients need to be monitored carefully for the possibility of failure or non-response.
00:19:58
Speaker
And then in that situation, again, as we would in non-COVID times, those patients should not encounter long delays to intubation and mechanical ventilation if they're failing these kinds of support modalities.
00:20:11
Speaker
Before we dive into talking about
00:20:13
Speaker
timing for intubation, which obviously is a very difficult topic, but I think a very important one.
00:20:18
Speaker
I wanna ask you specifically about two things related to non-invasive ventilation in general.
00:20:24
Speaker
One is reports obviously started in New York, but I think a lot of people have been observing this.
00:20:29
Speaker
Patients who might be on high flow nasal cannula who can cooperate, you ask them to prone themselves for a certain period of the time, and you might see improves in the pulse oximeter.
00:20:41
Speaker
Obviously, we don't know if this ultimately prevents people from being intubated, but it seems that the risk, obviously, in those who can cooperate is low.
00:20:50
Speaker
But any comments on this self-induced proning?
00:20:55
Speaker
Yeah, again, I think this is a promising intervention that's relatively simple, cheap, and could be widely
00:21:05
Speaker
administered in many health systems around the world if it's efficacious.
00:21:10
Speaker
And again, here's another good example of something that has been observed in many centers.
00:21:16
Speaker
And now we have a few case reports, two that were published in JAMA and one that was published in Lancet Respiratory Medicine by an Italian group.
00:21:23
Speaker
suggesting that there could be some short-term benefits, at least in the report published in one of the reports published in JAMA, there seems to be a short-term improvement in oxygenation, maybe not as profound in the other two studies, and some, again, conflicting reports about its ability to either delay or mitigate the need for intubation.
00:21:44
Speaker
in these patients.
00:21:45
Speaker
It seemed reasonably tolerated for short periods of time in these awake, non-intubated patients.
00:21:50
Speaker
So again, this is something now that seems to, there's some data suggesting it could be done.
00:21:56
Speaker
There's some data suggesting it has physiologic benefits and whether it has patient-important
00:22:01
Speaker
outcome changes needs to be discerned.
00:22:04
Speaker
And fortunately, there are at least a few now randomized control trials that are underway.
00:22:09
Speaker
And just to disclose, I'm on the steering committee of a Canadian trial that's looking at this being led by Waleed Alhazani and McMaster University, as well as a number of other clinical trials around the world.
00:22:19
Speaker
So hopefully we'll have some answers from randomized control trials on this specific question in this specific population in the near future.
00:22:29
Speaker
The second question I have, Eddie, is related to, I've seen more and more people sharing, these are not official reports in the literature, but sharing that they are utilizing salvage therapies such as inhaled nitric oxide in patients who are not intubated with the idea of rescuing them, in quotes, from, or preventing intubation.
00:22:54
Speaker
Any comments on this?
00:22:55
Speaker
Obviously, my interpretation that there's no data for this,
00:22:59
Speaker
But I just wanted to hear, I mean, what your thoughts were.
00:23:02
Speaker
Yeah, I think it's the same.
00:23:06
Speaker
idea here, I think without a lot of hard data suggesting that, you know, having inhaled vasodilators in these patients on high flow nasal cannula or non-invasive ventilation in terms of outcomes and maybe just delaying intubation in these patients, I would use the same criteria as we always have even in non-COVID patients and that if patients are feeling really conventional
00:23:34
Speaker
amounts of support with high flow nasal cannula or non-invasive ventilation that those patients would quickly move to being, again, consistent with their wishes and their goals of care to be intubated and placed on mechanical ventilation.
00:23:45
Speaker
I might try some of these strategies in those more elderly patients who, for instance, intubation and mechanical ventilation is not within their goals of care, i.e.
00:23:54
Speaker
they don't want to go to the intensive care unit or they don't want to be intubated and ventilated.
00:23:58
Speaker
I might try some of these rescue strategies in those patients on a case-by-case basis, but I think
00:24:03
Speaker
in patients where the plan of care would be to move to intubation if they were otherwise feeling high flow nasal cannula and non-invasive ventilation, I wouldn't try adding any inhaled vasodilators or that sort of thing and move quickly to intubating them and ventilating them in basically.
00:24:19
Speaker
So I think that in order to close this segment, it's fair to say that we have kind of moved from being very resistant because of infectious spreading concerns
00:24:33
Speaker
with the use of non-invasive to applying more non-invasive and understanding that there are some patients that with the proper monitoring could be treated with non-invasive, especially some of the younger patients.
00:24:44
Speaker
It might not need to be intubated, which might be a positive thing.
00:24:47
Speaker
But I think that the take home message should be that we should have all the precautions possible, but also we should be very vigilant of these patients because they're not improving or getting worse.
00:24:59
Speaker
we should probably find a different route in terms of a therapeutic approach for these patients and not delay the proper treatment.
00:25:07
Speaker
Agreed.
00:25:08
Speaker
Couldn't agree more.
Timing of Intubation in COVID-19 ARDS
00:25:09
Speaker
So let's dive into a difficult question, which is when should we intubate patients with COVID-19 ARDS?
00:25:17
Speaker
I think that we have never talked so much about when to intubate patients.
00:25:23
Speaker
I think that most clinicians have experienced the highest number of intubation days
00:25:28
Speaker
in their shifts with COVID.
00:25:33
Speaker
But I think that also this seems to be a pendulum where people are looking for absolutes.
00:25:37
Speaker
And I think it's a little bit more complicated than that.
00:25:40
Speaker
I think early on, people said early intubation.
00:25:43
Speaker
And some people took that, okay, if they require more than six liters, just go ahead and intubate them.
00:25:48
Speaker
Now people say we can avoid intubation, intubation associated with bad outcomes.
00:25:53
Speaker
And people have taken that to the other extreme and using all sorts of
00:25:56
Speaker
strategies to avoid putting somebody on a ventilator.
00:25:59
Speaker
And I imagine that at the end of the day, the way I interpret it, and I want to hear your thoughts, Eddie, is that people who need to be intubated should always be intubated early rather than late.
00:26:09
Speaker
The hard part is understanding who needs to be intubated.
00:26:12
Speaker
And that might be harder than it seems when you have so many patients with COVID.
00:26:16
Speaker
So what are your thoughts on intubation?
00:26:20
Speaker
Yeah, so I think I would separate it into two different considerations.
00:26:24
Speaker
So I think leaving aside what you spoke about last, Sergio, in terms of in the setting of a massive surge on hospital resources, where there are many patients and you might want to move to intubation earlier, I think those are system factors or organizational factors that might change your approach to intubation.
00:26:43
Speaker
But outside of that,
00:26:44
Speaker
I think thinking about patient factors that would sort of considerations that lead you to make a decision about intubation.
00:26:51
Speaker
Again, I would say that we in Toronto have been using the same strategy and the same considerations that we had used in non-pandemic times in patients with respiratory failure or impending respiratory failure and use the same criteria to assess them for the need for intubation.
00:27:09
Speaker
Now, again, we were fortunate in Toronto, so I can't speak from firsthand experience of
00:27:14
Speaker
that our hospital system was not overwhelmed with COVID patients on our wards, in our emergency departments to the point where we were managing hundreds of patients
00:27:23
Speaker
across our health system.
00:27:24
Speaker
So I can't speak from firsthand experience on that, but I think we try to employ the same strategies in these patients, recognizing, as many people do, clinicians do, that there are definitely risks of intubating patients, of all the procedure itself, then prolonged mechanical ventilation, ventilator-associated pneumonia, ventilator-induced lung injury, immobility, sedation, delirium, all the things that come with
00:27:49
Speaker
being on life support in the ICU.
00:27:51
Speaker
And again, so knowing, understanding these risks, you have to understand the trade-offs that are present in intubating these patients if they're failing conventional therapy.
00:28:00
Speaker
So we use the same strategy again that we sort of touched upon before in the patients who are failing otherwise conventional oxygen therapy or have a decrease in their level of consciousness so they can't protect their airway, they can't manage their secretions.
00:28:12
Speaker
The trajectory is accelerating, suggesting they're gonna have frank respiratory failure
00:28:17
Speaker
very quickly.
00:28:18
Speaker
There are technical reasons for why they can't have high flow nasal cannula or non-invasive ventilation.
00:28:25
Speaker
In these patients, just as we would in any other patient who has community-acquired pneumonia, aspiration, post-operative respiratory failure, we would move to intubate them.
00:28:34
Speaker
didn't really think too much about it being early versus late, then we consider these patients the same as any other patient with respiratory failure who was a candidate for intubation and mechanical ventilation.
00:28:48
Speaker
And then just to say again on the second point that I think, of course, this kind of a management strategy could require modification in those settings, in those pandemic settings where the hospitals under massive surge
00:29:03
Speaker
in which case, you know, you might consider shifting intubation to earlier times just because of human resources, management, and the sheer number of patients.
00:29:15
Speaker
But again, I would say those are separate organizational issues or system issues compared to the, you know, considerations for the individual patient.
00:29:22
Speaker
And I think that perhaps a lesson that people have learned, which again is not novel to COVID, but I think it's just, I mean, requires going back a little bit more in time,
00:29:34
Speaker
is the fact that hypoxemia per se, when people present, may not be the indication because you can treat hypoxemia with non-invasive, with supplemental oxygen at high levels.
00:29:46
Speaker
And that really it's like some other factors related to, I know Gattinoni and Dr. Marini have gone in the route of patient-induced lung injury, but really it's more about more of a respiratory failure that goes beyond just hypoxemia.
00:30:01
Speaker
And unfortunately, I hear like terms like happy hypoxemia being thrown around.
00:30:07
Speaker
If you are severely hypoxemic, you shouldn't be happy, I guess.
00:30:10
Speaker
So that might be an indication.
00:30:12
Speaker
But it reminds me, Eddie, to when I was in training with and we had a lot of HIV patients, patients who presented with PCP would be profoundly hypoxemic.
00:30:25
Speaker
But a lot of times with supplemental oxygen, they did okay.
00:30:29
Speaker
And we didn't have to just intubate them because they presented to the ED and their first SATs were in the 80s.
00:30:35
Speaker
So a lot of times you supplemented them with high oxygen and they were okay.
00:30:41
Speaker
But when they started developing other signs of refractory hypoxemia, obviously you need to move on and intubate some of these patients.
00:30:48
Speaker
Any thoughts on this as I think a unique feature of COVID that may not necessarily trigger an immediate intubation?
00:30:57
Speaker
No, I agree with you.
00:30:57
Speaker
And I think the PCP example is a good one.
00:31:00
Speaker
And I think of an important mantra in critical care as it is in probably clinical medicine is that we treat the patient and not the numbers.
00:31:07
Speaker
So exactly as you sort of described is that if the patient otherwise comes in with low oxygen saturation, which can be managed judiciously targeting modest oxygenation goals, the 88 to 93% say saturations, they're comfortable, their work of breathing isn't very high, they're awake, they're alert, they're interactive.
00:31:25
Speaker
they can manage their secretions and protect their airway, then these patients should be monitored and not rushed intubation because the PaO2 happens to be lower than you think it should be or the SATs are a bit lower than they should be.
00:31:36
Speaker
And I think this is something
00:31:37
Speaker
in general, in critical care, we've moved more and more towards a reliance on normalizing or treating these physiologic parameters or numbers.
00:31:46
Speaker
And what we really should do is to treat the patient.
00:31:48
Speaker
So I couldn't agree with you more that every patient is an individual.
00:31:52
Speaker
We should, obviously, these factors are important in the consideration for decision making around what kind of support they do or don't need.
00:32:00
Speaker
But at the end of the day, we need to treat the patient and not the numbers.
00:32:03
Speaker
Yeah.
00:32:04
Speaker
And I think that
00:32:05
Speaker
From my perspective, I mean, based on what you shared and what I've been able to learn and what I've seen in my practice, we should not forget that even in COVID patients, there are some indications like alteration in mental status, hemodynamic instability, that when present with respiratory failure, should probably push us towards intubation quicker.
00:32:26
Speaker
Further than that, I think that, like you said,
00:32:29
Speaker
and recognizing that when these patients are having a difficult or increased work of breathing or they're going in the wrong direction, maybe the time to pull that trigger also comes and that we should not think of intubation as a negative thing.
00:32:43
Speaker
It's one of the tools that we have.
00:32:45
Speaker
And the idea is to use the proper tools at the proper time.
00:32:50
Speaker
Exactly.
00:32:50
Speaker
It's the right tools for the right patient at the right time.
00:32:54
Speaker
So it's not, as you've mentioned many times, not a one size fits all.
00:32:57
Speaker
Yeah.
00:32:58
Speaker
So once they're intubated, obviously, they're on mechanical ventilation.
00:33:01
Speaker
And here I've also seen big swings in terms of how people reacted.
00:33:07
Speaker
Like at the beginning, some people were cranking up the PEEP, doing this, doing that.
00:33:11
Speaker
Then all of a sudden, people are not using almost no PEEP.
00:33:13
Speaker
And it seems to go from one extreme to the other.
00:33:16
Speaker
But why don't we take this segment to kind of refocus or go back to what we know about ARDS?
00:33:24
Speaker
I mean, we talked about
00:33:26
Speaker
possible phenotypes, but also in your viewpoint paper.
00:33:29
Speaker
And what we know is that a lot of the reported literature with COVID suggests that as a group, a lot of these intubated patients look very similar to other intubated patients with ARDS from other causes.
00:33:44
Speaker
Is that correct?
00:33:46
Speaker
Yeah, I think, you know, looking again, and the numbers are growing, but at the time of publication, we included a number of published cohorts,
00:33:54
Speaker
that provided mechanical ventilation parameters and respiratory mechanics on patients.
00:33:58
Speaker
So a few from New York, some originally from China, and then some from the United States, and one from Europe, that showed on average the respiratory system compliance in these patients when it was measured was very similar to those that were previously enrolled in clinical trials or observational studies of ARDS.
00:34:17
Speaker
So these patients in the end, on average, looked very similar to patients in previous
00:34:23
Speaker
ARDS cohorts.
00:34:25
Speaker
And again, until we have, which is improving again, more data, more rigorous data specifically on COVID-19 induced ARDS.
00:34:35
Speaker
I mean, our best strategy is to extrapolate all the data
00:34:41
Speaker
and management approaches that we have gleaned over more than 50 years of research on ARDS.
00:34:48
Speaker
Because at the end, these patients and a number of autopsy series now also confirm that in the end, at least the respiratory pathology looks a lot like ARDS.
00:34:59
Speaker
There definitely now is, of course, an emerging amount of data that shows that the virus also has a number of
00:35:06
Speaker
Pneotropic effects on other organ systems in particular, I think highlighted has been disruptions in coagulopathy, maybe there's an associated endothelialopathy and an increased number of thrombotic events.
00:35:18
Speaker
So these are important, maybe new feature of COVID, but at least when it affects the lungs,
00:35:23
Speaker
at autopsy, it looks like diffused alveolar damage and ARDS.
00:35:28
Speaker
So I think our overriding mantra in thinking of the management of a ventilated patient is to treat them like we've treated or ventilate them as we've always ventilated ARDS patients and use that as the starting point.
00:35:40
Speaker
And I think it's also important to, and one of the things that I really enjoyed about the viewpoint, I mean, in terms of its approach was the balance, right, in the scientific kind of openness to say that
00:35:52
Speaker
if I describe 100 white swans, it doesn't prove that there's not a black swan somewhere, right?
00:35:58
Speaker
And I think that we do recognize that there might be phenotypes depending on when they present, but on average, what we're seeing now in our hospitals, it looks similar with its variations to what we saw in other patients with ARDS.
00:36:12
Speaker
And I think it's good to remind people what we've learned so far in ARDS.
00:36:17
Speaker
And I think we could start, Eddie, with what's the only
00:36:22
Speaker
A1 recommendation from everything that we're talking about today, which is low tidal volumes.
00:36:28
Speaker
And that means that basically it's a strong recommendation based on one or more randomized trials.
00:36:34
Speaker
And maybe we could start by just talking about tidal volume in patients who are intubated with COVID-19 induced ARDS.
00:36:42
Speaker
Yeah, so again, following on the recommendations that we have in place for the ventilatory management of ARDS patients in general, low tidal volume ventilation, as you mentioned, is really the cornerstone of the ventilatory management of these patients.
00:36:58
Speaker
And so again, the starting tidal volume in these patients should be six mils per kilo predicted body weight, which can be either reduced if plateau airway pressures remain high.
00:37:10
Speaker
So for the ARMA trial, we know that 30 is
00:37:13
Speaker
at least a marker of high airway pressure.
00:37:19
Speaker
So if that's six mils per kilo, the platelet pressure is still about 30, you can reduce tidal volume down to as low as four mils per kilo.
00:37:26
Speaker
And if the patient is having, you know, asynchrony and discomfort from six mils per kilo tidal volumes and the platelet pressure is still low, then you can consider liberalizing tidal volume to as high as eight mils per kilo.
00:37:41
Speaker
again, the cornerstone of the ventilatory management then again for all ARDS patients being this use of pressure volume limited lung protective ventilation.
00:37:51
Speaker
And can you mention a little bit, I mean, what we know in non-ARDS patients in low tidal volumes and how they protect or don't protect the lung?
00:38:00
Speaker
Yeah, so increasingly, I think, you know, we're having more and more reports from other populations of non-ARDS patients suggesting that
00:38:12
Speaker
a potential benefit of using these kinds of low tidal volume strategies, even those in patients who don't have established ARDS but might be at risk.
00:38:20
Speaker
So we now have a few randomized control trials and observational studies looking at patients, say the intraoperative management.
00:38:26
Speaker
So even patients being ventilated for a short period of time following thoracic surgery or abdominal surgery,
00:38:32
Speaker
employing these lower tidal volumes than traditional.
00:38:35
Speaker
And some of the post-operative management of these patients using low tidal volumes seem to lead to a reduction in pulmonary complications and progression to ARDS when you use these protective strategies.
00:38:46
Speaker
So again, I think
00:38:49
Speaker
increasingly overall in the field, it seems that not only is the use of lung protective ventilation a good idea in ARDS, but it might also be a very good idea in patients at risk or who don't have established ARDS.
00:39:04
Speaker
And I think maybe the most important consideration, again, from a health system point of view is that we know from the LungSafe study that very many patients are being under-recognized by clinicians for ARDS.
00:39:14
Speaker
And only two-thirds of patients are getting what we would consider lung-protected ventilation in terms of tidal volume and plateau pressure in ICUs around the world.
00:39:23
Speaker
And if you sort of just use a strategy where any ventilated patient, at least the starting point, would be six mil per kilo tidal volumes, then you might mitigate some of the challenges of under-recognition or those who might even be recognized who are not receiving low tidal volume ventilation to get that therapy and then individualize based on the patient's characteristics from there.
00:39:44
Speaker
And I think that's important because, like you said, I mean, it's a range, right, from four to eight.
00:39:48
Speaker
You start at six, but you can individualize and move one way or the other based on what you're seeing with the patient that you're treating at the bedside.
00:39:57
Speaker
The other question I had.
00:39:59
Speaker
Go ahead.
00:39:59
Speaker
Yep, go ahead, sir.
00:40:00
Speaker
No.
00:40:01
Speaker
The other question I had, Eddie, is could you comment how driving pressure fits into this?
00:40:10
Speaker
Yeah, so driving pressure is a, I think, an increasingly interesting and potentially important ventilatory parameter to consider.
00:40:22
Speaker
I think the challenge, of course, is that it's again, it's very appealing from a physiologic point of view.
00:40:26
Speaker
So driving pressure representing the tidal volume that's scaled to respiratory system compliance so that the worse, the more
00:40:35
Speaker
stiff your lung is, so the worse the respiratory system compliance, the less you would want the tidal volume delivered to the baby lung and therefore that could be reflected by a lower driving pressure.
00:40:46
Speaker
The challenge is of course at the present time we only have an observational study
00:40:50
Speaker
a very high-profile observational study from Marcelo Amato and colleagues published in the New England Journal that looked at a post hoc analysis of randomized controlled trial data to establish that lower driving pressures were associated with lower mortality in patients with ARDS.
00:41:03
Speaker
And there seemed, at least from the data, that maybe there's a threshold around a driving pressure of 15, where mortality really started to increase steeply.
00:41:14
Speaker
So now what we need is that, again, this is an interesting, much like the proning in awake non-intubated patients, is an interesting observation.
00:41:21
Speaker
It has a strong physiologic rationale.
00:41:23
Speaker
And now we need to test that in a randomized
00:41:27
Speaker
clinical trial.
00:41:27
Speaker
So fortunately, the Brazilians have moved from this observational study, they've published some phase two data showing the feasibility of a driving pressure limited strategy.
00:41:37
Speaker
And now we need some confirmatory clinical trials to show that a strategy focused mainly on reducing driving pressure is going to be one beneficial and two, if it's any different or better than reducing tidal volume.
00:41:51
Speaker
One of the main ways of reducing driving pressure is to reduce tidal volume.
00:41:55
Speaker
One of the things I'm hopeful to see is that whether actually a strategy limiting driving pressure leads to really any different ventilatory settings than a strategy that limits tidal volume like we use now.
00:42:07
Speaker
So I think it's interesting, but we need more data.
00:42:11
Speaker
And just to share with the audience, I mean, by driving pressure, we're just talking about plateau pressure minus the PEEP.
00:42:19
Speaker
And the thought is that you're adjusting it based on changing your tidal volume
00:42:23
Speaker
and having an impact on your plateau pressure, correct?
00:42:26
Speaker
Yes, yeah.
00:42:28
Speaker
Excellent.
00:42:30
Speaker
So any thoughts on hypercapnia?
00:42:33
Speaker
That is always obviously something that people struggle with.
00:42:35
Speaker
I mean, obviously, in the old days, we talk about permissive hypercapnia, but this is something also that I think that people have proposed as maybe a reason to liberalize a little bit in terms of the tidal volume.
00:42:49
Speaker
But any thoughts on how you would approach hypercapnia in these patients?
00:42:54
Speaker
Yeah, again, I think similarly, I think again from the ARDS literature, I think what we would do is for these mechanically ventilated patients, again, target modest physiologic goals.
00:43:07
Speaker
So targeting oxygen saturations of 88 to 93%, like in the ARMA trial and targeting that pH.
00:43:15
Speaker
So which is related to the presence of hypercapnia and respiratory acidosis of above 7.25, which again is a trade-off.
00:43:23
Speaker
against increasing intensity of mechanical ventilation and the risk of more ventilator-induced lung injury, which we think is a main driver of multi-organ failure and outcomes in patients who are ventilated with the RDS.
00:43:37
Speaker
So the trade-off here is to tolerate modest intensity mechanical ventilation, which as a consequence leads to some permissive hypercapnia.
00:43:46
Speaker
So as long as the pH
00:43:48
Speaker
for our patients is about 7.25 from the resulting respiratory acidosis.
00:43:54
Speaker
That's the kind of hypercapnia we would tolerate.
00:43:55
Speaker
And it's very similar to the limits that were tolerated in the ARMA trial from the ARDS network.
00:44:04
Speaker
again, which could be individualized in patients where there might be other considerations for managing hypercapnia more tightly.
00:44:11
Speaker
So, you know, patients who have intracranial hypertension, patients who are pregnant, these sorts of things, special considerations.
00:44:17
Speaker
But otherwise, in the absence of contraindications, we would allow some permissive hypercapnia and target a pH above 7.25.
00:44:24
Speaker
Excellent.
00:44:25
Speaker
So let's move on to PEEP, which obviously is a little bit more difficult, maybe in tidal volume, because we don't have as much literature.
00:44:32
Speaker
But I think that
00:44:33
Speaker
In general, it seems, Eddie, that people have moved from either high PEEP or low PEEP just to kind of as a dichotomy with COVID.
00:44:43
Speaker
And the reality is at the end of the day, what we're trying to identify is what's the best PEEP for that patient.
00:44:48
Speaker
And obviously that sometimes can be difficult, but why don't you share with us what evidence suggests and what your approach is to using PEEP in these patients?
00:44:57
Speaker
Yeah, so I think, again, our approach is no different than what we recommended in our ATS, EDS, ICM, SCCM guideline for ARDS patients, is that as the patient becomes more hypoxemic, so as they progress from, say, mild to moderate to severe ARDS, we would try to apply higher levels of PEEP in patients who have more severe lung injury, as the data suggests.
00:45:23
Speaker
The challenge, of course, is, as you said, is twofold.
00:45:26
Speaker
One is, what is higher PEEP?
00:45:28
Speaker
And two, how do you set it?
00:45:30
Speaker
And these are challenges that, of course, in the field, and again, to quote Professor Gattinoni, who gave a lecture on this when I was a fellow in Brussels, said at the time, after 40 years of research, we still don't know how to set PEEP.
00:45:43
Speaker
I would say that's still as relevant today as it was
00:45:46
Speaker
when I heard that message over 15 years ago.
00:45:49
Speaker
But I think as a starting point, again, we could use strategies from large randomized control trials that have been published.
00:45:57
Speaker
So for instance, the alveoli trial, which used the PEEP-FO2 table, the express study, which tried to maximize PEEP to achieve a maximum plateau pressure of about 28 centimeters of water, or LELPS, which also use a different high PEEP-FO2 table.
00:46:14
Speaker
So those might be a starting point
00:46:16
Speaker
for setting PEEP.
00:46:17
Speaker
We're now getting data on other tools that might be available at the bedside depending on your center's comfort with them.
00:46:23
Speaker
So things like electrical impedance tomography might be a way to understand, again, the trade-offs between overinflation or overdistension and underinflation in some areas or at electasis by changing PEEP
00:46:38
Speaker
using esophageal manometry.
00:46:41
Speaker
One of my colleagues here in Toronto, Laurent Bruchard, has recently published on this recruitability index, which might be also a simple bedside maneuver to test response to higher or lower levels of PEEP.
00:46:51
Speaker
So there could be ways to try to gauge the individual patient response, but that's the key.
00:46:55
Speaker
I think using any of these tools as a starting point to set the PEEP and then trying to individualize PEEP
00:47:01
Speaker
to that patient's respiratory mechanics is the key.
00:47:03
Speaker
And some of those patients are going to tolerate higher PEEP, and some of those patients are going to be less recruitable and not tolerate higher PEEP.
00:47:10
Speaker
And that is the individualization of the strategy in those patients.
00:47:15
Speaker
And in terms of what we understand or what we believe PEEP responses, in general, could you comment on the concept of patients who have higher recruitability might
00:47:29
Speaker
benefit or respond to higher PEEP versus patients who have lower recruitability might be harmed and what are the potential harms of PEEP?
00:47:38
Speaker
Yeah, I think, you know, so maybe two, you know, there are a few potential negative effects to PEEP, maybe two to highlight are, again, over distension.
00:47:51
Speaker
So the possibility of over distension injury on the lung where the PEEP is being applied, higher PEEP is being applied.
00:47:59
Speaker
And second is hemodynamic effects.
00:48:02
Speaker
because again, as the PEEP increases and intrathoracic pressure increases, that might have deleterious effects on intrathoracic structures like the heart,
00:48:10
Speaker
and some of the major vessels limiting either venous return or cardiac output.
00:48:15
Speaker
So there could be hemodynamic consequences to higher PEEP.
00:48:17
Speaker
And here again is a very interesting heterogeneity, if you will, that Professor Gattinoni describes quite a few years ago in the New England Journal showing that, again, typically patients who have, through CT scanning, who have less severe lung injury, very little collapsed lung,
00:48:34
Speaker
on their CT scan, they have low recruitability because there's not a lot of collapsed lung to recruit in those patients.
00:48:39
Speaker
So if you apply high PEEP to those patients, all that happens is that the healthy lung units or relatively healthy lung units get over-distended, intrathoracic pressure increases, that squishes the heart and the great vessels, and you get hemodynamic compromise, over-distension, which might lead to desaturation.
00:48:54
Speaker
So you get complications.
00:48:55
Speaker
Whereas in CT scans of severe ARDS patients, where there's a lot of collapsed
00:49:01
Speaker
lung tissue, that collapsed tissue has the potential to be recruited.
00:49:04
Speaker
So these might be the patients that respond to higher PEEP.
00:49:07
Speaker
And because recruitment then actually leads to a drop in pleural pressure, you don't get the hemodynamic compromise, you actually get increased surface area of lung available for gas exchange and perhaps an improvement in both oxygenation and ventilation in those patients.
00:49:20
Speaker
So here is again, an example of heterogeneity that Professor Gattinoni published in the New England Journal, showing that these both ARDS patients, but they respond differently to
00:49:33
Speaker
Excellent.
00:49:33
Speaker
So before we go into some salvage therapies, I wanted to ask you about modes of ventilation.
00:49:39
Speaker
I think that there obviously has always been, I mean, a lot of enthusiasm amongst our critical care colleagues for different nontraditional modes of ventilation.
00:49:49
Speaker
I know that your group has been instrumental in studying high frequency oscillation ventilation, and that didn't pan out to probably work as well for ARDS, but also
00:50:00
Speaker
I see and read a lot about people proposing the use of APRV in these patients.
00:50:05
Speaker
I know that in the last iteration of the consensus statements, you did not comment on APRV specifically, but any thoughts?
00:50:15
Speaker
Yeah, I think at this point, again, in the absence of high-quality data, it's hard to know what to do with alternative modes of ventilation.
00:50:23
Speaker
I think certainly, as you mentioned, much to our...
00:50:28
Speaker
surprise that high-frequency oscillation, which is something that was near and dear to our hearts in Toronto, didn't seem to be beneficial.
00:50:36
Speaker
And certainly there was a signal towards harm in the oscillate study.
00:50:38
Speaker
So we've abandoned, largely abandoned, the routine use of high-frequency oscillation in these kinds of patients.
00:50:47
Speaker
In terms of APRV, I think this has been a challenging situation.
00:50:50
Speaker
I think there's a lot of...
00:50:54
Speaker
support for this mode of ventilation as being potentially beneficial.
00:50:57
Speaker
I think the challenge has been is that there's unfortunately not been a lot of high quality data and really no large scale randomized controlled trial comparing it to the standard of care showing a benefit.
00:51:09
Speaker
And so I think, again, this is not to say, as you mentioned before, that
00:51:14
Speaker
absence of evidence isn't evidence of absence.
00:51:17
Speaker
It's just that we need data.
00:51:19
Speaker
So it could actually be something very useful, but we just need to study it.
00:51:23
Speaker
And so again, what I would hope that my colleagues who are strong components of APRV is that maybe to get together and collaborate on a trial to demonstrate the potential benefit of that mode.
00:51:36
Speaker
But in the setting of this pandemic, I would say, as I often say to many people, is that you should do what you know best.
00:51:40
Speaker
This is probably not the right time to engage in, you know, sort of a potpourri of alternative modes and stick with what you know best.
00:51:48
Speaker
If that's volume control for controlled ventilation and then pressure support for assisted ventilation, then stick with those.
00:51:55
Speaker
And until we have data that other modes do anything more or better than those, I would just stick with what you know.
00:52:01
Speaker
Yeah, and I think that my observation of the use of APRV
00:52:06
Speaker
Obviously, like you said, I mean, it's possible that it's better.
00:52:10
Speaker
We just don't know.
00:52:11
Speaker
It's possible that it hurts.
00:52:12
Speaker
We don't know again.
00:52:13
Speaker
But the two things that I have found, Eddie, that concern me are one is that I think clinicians, when they go down the APRV route, are optimizing for oxygenation and are not really paying attention to the things that we know make a difference, which are
00:52:29
Speaker
lung protective ventilation in terms of understanding what the tidal volume really is and what are the pressures that we're really imposing or the stress and strain on that lung.
00:52:38
Speaker
And I think that is a little bit concerning to me.
00:52:40
Speaker
And the second thing which you mentioned is that no matter how good you think you understand APRV, in many hospitals, there's a lot of other people involved like respiratory therapists or other clinicians that are cross-carving that might or might not be as comfortable.
00:52:55
Speaker
And maybe, like you said, when you have such a big number of patients,
00:52:58
Speaker
trying new things is not at the right time.
00:53:00
Speaker
Any comments on those?
00:53:02
Speaker
Yeah, I think I agree with both of those statements.
00:53:05
Speaker
I think this is part of the challenge is to remember that the vast majority of patients with ARDS don't die of refractory hypoxemia.
00:53:13
Speaker
And in fact, we have a lot of studies showing that oxygenation is not a good surrogate for mortality in ARDS.
00:53:18
Speaker
And again, a good example is that in the ARMA study,
00:53:21
Speaker
the low tidal volume arm had actually worse oxygenation on day one than the control group, but they ultimately were the group that had the 9% absolute risk reduction in mortality.
00:53:32
Speaker
So optimizing oxygenation may not, except in those very few patients who were actually dying of hypoxemia, be a very good surrogate for outcomes, but reducing ventilator-induced lung injury, as you said, and focusing on things like tidal volume, airway pressures, and that is important.
00:53:47
Speaker
And two, I think, again, agreed, like when your resources are stretched thin,
00:53:53
Speaker
unless there's compelling evidence that we need to do X because we've just demonstrated that X is saving these patients' lives.
00:53:58
Speaker
I think trying to establish a new system of interventions during a pandemic is maybe not the best time to do that.
00:54:08
Speaker
Let's talk about prone positioning in intubated patients.
00:54:11
Speaker
I think that, like you mentioned earlier, this is an example of a therapy that had a physiological underpinning rationale
00:54:20
Speaker
that was tested and didn't really show great improvements till we kind of fine-tuned who are the right patients for this, which is moderate to severe ARDS patients.
00:54:30
Speaker
But clearly, I think that we have seen a widespread adoption of proning in many ICUs with COVID.
00:54:37
Speaker
And I have, for my own practice, seen a lot more prone patients on a regular basis than I would see maybe in non-COVID times.
00:54:45
Speaker
But could you talk a little bit about prone positioning and ARDS from COVID?
00:54:49
Speaker
Yeah, I think similar to our discussion about the other therapies, that this is something that we now understand has a dramatic benefit in patients with moderate to severe ARDS.
00:55:00
Speaker
So I think it's an intervention that in the absence of contraindication should be applied similarly to moderate to severe COVID-associated ARDS and hopefully would have the same
00:55:12
Speaker
benefits.
00:55:13
Speaker
And I think, again, here's another important point to highlight that prone positioning is really not a rescue strategy to improve oxygenation in those with refractory hypoxemia.
00:55:21
Speaker
We think one of the main benefit of prone positioning is that it leads to more homogeneous distribution of ventilation, which leads to a reduction in ventilator-induced lung injury, and then that leads to a mortality
00:55:33
Speaker
benefits.
00:55:34
Speaker
So, oxygenation, again, is not the key thing that we're trying to improve with prone positioning.
00:55:38
Speaker
It's really trying to protect another strategy to help protect the lung when the lung is severely injured.
00:55:43
Speaker
And from that perspective, obviously, early intervention would make sense, right?
00:55:47
Speaker
In terms, I mean, if you intubate somebody, they're very sick, I mean, they meet the criteria, not waiting too much time to start the prone position interventions.
00:55:59
Speaker
Agreed.
00:56:00
Speaker
Exactly.
00:56:01
Speaker
Now, could you comment, Eddie, on the timing of the prone position itself?
00:56:06
Speaker
Clearly, obviously, we have learned that the trials, I think the recommendation really usually gives us the floor, so 12 hours or more.
00:56:16
Speaker
But I think that what we've seen based on anecdote and reports from around the world is that some of these patients are left in the prone position maybe longer than
00:56:27
Speaker
And I think that we obviously don't know what the exact recipe should be, but it does seem that COVID patients are being prone for longer turns and for more turns than non-COVID ARDS patients.
00:56:42
Speaker
Any comments on this?
00:56:44
Speaker
Yeah, I think that's probably true.
00:56:47
Speaker
I think in our ICU, we were attempting to prone patients closer to the Proceva study protocol, which was keeping them in the prone position if possible for 16 to 18 hours a day, and then giving them a break on their backs that they would tolerate that.
00:57:01
Speaker
I think, again, we just need to be cognizant that there are complications from prolonged proning, including
00:57:05
Speaker
facial edema, pressure sores and ulcers in sort of non-traditional areas depending on how you're supporting.
00:57:10
Speaker
So shoulder girdle, hip girdle, facial edema and facial breakdown, these sorts of things.
00:57:18
Speaker
So if possible, you want to try to get them out of the prone position if they would tolerate it.
00:57:22
Speaker
And again, I would say at least anecdotally, and hopefully more evidence on this is coming out soon, we definitely had many COVID patients in our ICU who were prone for a prolonged period of time, more than a week, sort of receiving daily prone sessions.
00:57:36
Speaker
Recall that in the Proceva trial, the median number of proning sessions was about four and a half days or four and a half sessions.
00:57:43
Speaker
So we certainly in our ICU saw patients that had more
00:57:48
Speaker
than that proning and those were concentrated in the ones with a very severe COVID associated ARDS.
00:57:57
Speaker
And for an individual turn, have you had experience with keeping people prone longer than 18 hours?
00:58:03
Speaker
Yeah, so we had some, you know, again, we had some very severely ill COVID-associated ARDS patients who had good responses to prone positioning who, you know, we'd flip them supine and they might last, you know, an hour or two before their gas exchange became
00:58:23
Speaker
less manageable and we would just flip them back to the prone position in that situation.
00:58:27
Speaker
So we definitely had some patients who really tolerated little and some maybe no sort of turning to the supine position for a few days.
00:58:37
Speaker
What about the use of neuromuscular blockers?
00:58:39
Speaker
And that's something that obviously the initial French study suggested would be very beneficial for a short period of time in non-COVID severe ARDS.
00:58:48
Speaker
And then a follow-up study suggested that may be not as effective.
00:58:52
Speaker
And I think that we're still trying to figure out what's the right patient.
00:58:55
Speaker
But my sense is that because of the proning, because of how sick they are, there's more patients with COVID who are receiving neuromuscular blockers than our usual ARDS patients.
00:59:06
Speaker
Yeah, I think again, the data, at least in my center, I would say that's probably true.
00:59:11
Speaker
I would say almost all of our patients in the ICU who are receiving these kinds of therapies for severe COVID-related RDS, like proning, some that got onto ECMO, some that were in very high levels of mechanical ventilation were also deeply sedated and paralyzed.
00:59:25
Speaker
Again, to reduce oxygen demand, to facilitate
00:59:32
Speaker
mechanical ventilation and prevent asynchrony.
00:59:35
Speaker
And also in some of these patients when they were on lighter sedation and off paralysis, they seem to have a very high respiratory drive.
00:59:45
Speaker
So again, and worrying about the possibility of perpetuating lung injury, especially in these severe patients.
00:59:51
Speaker
So at least in our experience, I would agree with your statement that we definitely had a large proportion of our severe
00:59:58
Speaker
COVID patients with ARDS deeply sedated and paralyzed for longer than we usually would in other ARDS patients.
01:00:06
Speaker
Any comments on salvage therapy with inhaled vasodilators?
01:00:10
Speaker
We talked a little bit about nitric oxide earlier, but obviously from our experience in ARDS, I mean, these might be utilized for rescue and refractory hypoxemia, but studies have never shown that they actually improve mortality.
01:00:24
Speaker
But any thoughts on this, Eddie, in terms of how you approach it?
01:00:29
Speaker
Yeah, so in our unit, in our ICU, which is an ECMO center as well, we've really gone away from using, I would say, inhaled nitric oxide in ARDS patients who develop refractory hypoxemia unless they develop a specific indication for
01:00:47
Speaker
inhaled nitric oxide, for instance, if they have very severe right heart failure, pulmonary hypertension that we think might be, you know, an important cause or at least contributing to their hypoxemia, in which case maybe a trial of inhaled nitric oxide would be useful.
01:01:01
Speaker
But for the general sort of refractory hypoxemia patients, we've really stopped using inhaled nitric oxide in these patients and would move quickly if they were failing the prone position to Vino-Vino ECMO.
01:01:16
Speaker
So, but there have been quite a few COVID patients that we received that were, for one reason or another, not candidates, for instance, for VV ECMO, in which, again, as a salvage therapy, when they became high-loxemic, we tried nitric oxide in.
01:01:30
Speaker
Surprisingly, I would say quite a few of our patients who did receive it had a dramatic improvement in their oxygenation.
01:01:39
Speaker
Again, we just need to collect that data and look at it more systematically, but at least anecdotally, we did have quite a few COVID patients have a pretty robust response from an oxygenation standpoint to the use of inhaled nitric oxide.
01:01:52
Speaker
Excellent.
01:01:53
Speaker
And I think we could probably dedicate a whole episode to ECMO, and I know this is one of your passions.
01:01:59
Speaker
But also, I think that maybe just some comments recognizing that not all places are ECMO centers and that ECMO is a limited resource, and especially in places or in communities where there is a large burden of COVID patients, it might be impossible to provide ECMO to all the patients that we want to provide.
01:02:18
Speaker
But what are your general thoughts in terms of how you're approaching ECMO for COVID-19 induced ARDS?
01:02:25
Speaker
So we approached it similarly to, again, to non-COVID patients.
01:02:32
Speaker
Our starting point would be EOLIA entry criteria.
01:02:35
Speaker
So despite optimal mechanical ventilation, a trial of prone positioning, these patients are still either quite hypoxemic or have respiratory acidosis and hypercapnia as per the inclusion criteria from EOLIA.
01:02:50
Speaker
And we use the same kinds of considerations.
01:02:53
Speaker
So age less than 65 that our program uses for non-COVID ARDS patients, we evaluate their comorbidities, the presence of multi-organ failure, how long they've been ventilated for, how reversible we think the underlying situation is.
01:03:09
Speaker
And of course in COVID patients, we had some additional considerations for comorbidities that traditionally wouldn't exclude you for ECMO consideration, but we understood in COVID led to a poor prognosis, things like obesity, hypertension, preexisting cardiac disease.
01:03:25
Speaker
So we considered those factors as well.
01:03:28
Speaker
And we, as you mentioned, tried to be judicious about its use in the preparation for the potential surge in our jurisdiction.
01:03:37
Speaker
But basically, again, just use the same criteria we would for non-COVID ARDS patients, maybe with those few extra considerations for comorbidities that we recognize in COVID patients were important prognostic factors.
01:03:54
Speaker
Excellent.
01:03:54
Speaker
So I think that obviously we could also spend a lot of time talking about weaning of these patients, but I think that for
01:04:03
Speaker
respecting your time and also we'll have future episodes of the podcast that will focus on, on weaning aspects.
01:04:09
Speaker
But, um, I do want to, want to stop here with the ARDS discussion, Eddie.
01:04:14
Speaker
And one of the things that we traditionally do with critical matters is at the end, we ask our guests a couple of questions unrelated to the topic, just to tap into their, their wisdom and try to learn from them.
01:04:24
Speaker
Would that be okay?
01:04:26
Speaker
Yeah, that sounds great.
01:04:27
Speaker
I don't know about wisdom, but I could give you some answers.
01:04:31
Speaker
Awesome.
01:04:32
Speaker
So the first question relates to books and are there any books or book that have influenced you significantly or that you have gifted most often to others?
01:04:42
Speaker
Yeah, so I would say that in high school, I really developed a passion for English literature.
01:04:47
Speaker
In fact, one of my English teachers, one of my formative first mentors in high school and the book that opened it up for me was James Joyce's book called Portrait of the Artist as a Young Man.
01:04:58
Speaker
James Joyce is my favorite
01:04:59
Speaker
author and I've often tried to gift this book to some of my friends and colleagues.
01:05:05
Speaker
It's a bit of a dense little novel, but extremely rich with philosophy and life outlook.
01:05:15
Speaker
Yeah.
01:05:16
Speaker
And I think that it's interesting because a lot of people would say that reality is really found in fiction, right?
01:05:23
Speaker
I mean, and it's really the study of human nature.
01:05:26
Speaker
And yeah, I mean, I can imagine that for some people, James Joyce in an era of Twitter might be a little bit of a stretch in terms of density and effort, but definitely worth the effort.
01:05:36
Speaker
And we'll definitely link this one to the show notes.
01:05:42
Speaker
The second question, Eddie, relates to something that you believe to be true in medicine or in life that many others don't believe or at least act as they don't believe.
01:05:52
Speaker
Yeah, I think the thing that I try to instill in the residents, the health staff and the team about the practice of medicine and is true in life is this idea is the golden rule.
01:06:03
Speaker
Like do unto others as you would have them do unto you and to treat patients as you would want your family members or yourself to be treated.
01:06:09
Speaker
I think if we use that
01:06:11
Speaker
lens more often, we would be, you know, we'd have a very good framework for how to treat these vulnerable, critically ill patients, their family members, their surrogates.
01:06:22
Speaker
I think if we treated them as we would want to be treated or we want our mother, father, brother, sister to be treated, I think that would go a long way.
01:06:29
Speaker
And I think it's also a very appropriate and fitting thought for what's going on in many hospitals.
01:06:37
Speaker
I think that we obviously are concerned about our patients.
01:06:41
Speaker
But it seems that with COVID, there's more and more barriers between us and our patients as human beings.
01:06:47
Speaker
The fact that their families are not there, the fact that we're all in PPE, the fact that a lot of these people, I mean, obviously, can't communicate as well, I think has potentiated this.
01:06:58
Speaker
And I think it's a great reminder of how we would want our loved ones to be treated if they were in that situation.
01:07:07
Speaker
I agree.
01:07:07
Speaker
I think it's been, it's obviously been challenging for everyone.
01:07:11
Speaker
And I think maybe recognize taking a moment to recognize that it's been hard for healthcare workers, but it's been hard for families, hard for the patients, obviously who have COVID and are sick.
01:07:20
Speaker
It's been hard on patients who even don't because of the effects on our economy and society.
01:07:24
Speaker
And so I think, I think the more that we could sort of take a moment and reflect and then try to use, you know, some sympathy, kindness and empathy for the fact that everybody's having a hard time and then moving forward from their
01:07:36
Speaker
would really help.
01:07:38
Speaker
And the last question, Eddie, relates to what would you want every intensivist or advanced practitioners listening to us today to know?
01:07:47
Speaker
Could be a quote or a fact or just a parting thought.
01:07:50
Speaker
I think it's the growing idea that less is more.
01:07:56
Speaker
I think especially in the ICU, that soberingly for all the things that we've tried to study and understand, in the end, it seems that they typically interventions cause more harm than good and that less is more.
01:08:07
Speaker
And the whole choosing wisely movement is that we should choose wisely so that, you know, as we've talked about in this podcast, which has been great,
01:08:16
Speaker
is that being at the bedside is important.
01:08:18
Speaker
Details matter in critical care.
01:08:20
Speaker
And so watching carefully and often just standing there and doing nothing rather than don't just stand there, do something, will go a long way for our patients.
01:08:29
Speaker
So I think less is more is an important mantra in the care of critically ill patients.
01:08:35
Speaker
And I think that's a great place to stop.
01:08:37
Speaker
I want to thank you, Eddie, for your time and being so generous with sharing your thoughts and your knowledge with us.
01:08:43
Speaker
We'll definitely link a lot of the articles that we've mentioned throughout the conversation in our show notes.
01:08:51
Speaker
I hope that you're doing well in Toronto.
01:08:54
Speaker
It's hard to believe that you're still the reigning champions of the NBA, right?
01:08:59
Speaker
We are at the moment, yes.
01:09:02
Speaker
It seems like that was like decades ago.
01:09:04
Speaker
But I hope things get back to where we want them to be and that we have a chance to interact in person again.
01:09:12
Speaker
And I hope to have you back on the podcast.
01:09:14
Speaker
Thank you very much.
01:09:16
Speaker
I appreciate it.
01:09:16
Speaker
Thank you.
01:09:17
Speaker
Please stay safe, everyone.
01:09:20
Speaker
Thank you for listening to Critical Matters, a Sound Critical Care podcast.
01:09:25
Speaker
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01:09:31
Speaker
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01:09:36
Speaker
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