Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now your host, Dr. Sergio Zanotti.
Speaker: In today's podcast episode, we will discuss respiratory support in ARDS.
Speaker: We will base our discussion on the most recent clinical guidelines published by the European Society of Intensive Care Medicine in 2023.
Speaker: Our guest is Dr. Eddie Fan.
Speaker: Dr. Fan is 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.
Speaker: He is currently the medical director of the Extracorporeal Life Support Program, the Toronto General Hospital, and the director of critical care research at the University Health Network, Mount Sinai Hospital.
Speaker: Dr. Fan's research has focused on advanced life support for acute respiratory failure and patients' outcomes from critical illness.
Speaker: Dr. Fan is a co-author of the European Society of Intensive Care Medicine guidelines we will discuss today.
Speaker: It's a true honor to have him back on the podcast.
Speaker: Eddie, welcome back to Critical Matters.
Speaker: Yeah, thank you, Sergio, for the kind invitation.
Speaker: Really happy to be here.
Speaker: So I would like to start maybe with just some general comments on your part.
Speaker: You were part, obviously, of the task force that looked at these guidelines.
Speaker: But more importantly, as we've had you before on the podcast, you're really invested in being a clinical scientist in the realm of ARDS.
Speaker: So really always doing research and staying up to date with what's important.
Speaker: So just give us some general comments on these recent guidelines.
Speaker: Yeah, so thanks for the opportunity to speak about this important work.
Speaker: First, I want to just credit the chairs of this new guideline for the European Society of Intensive Care Medicine.
Speaker: So Drs.
Speaker: Grisele, Calfi and Camporota, who really led a very large group of international experts to the creation of this guideline.
Speaker: And maybe the key sort of overarching thing to mention about this is they're exactly that.
Speaker: They're guidelines, right?
Speaker: They're not hard and fast rules that apply in every situation to every patient.
Speaker: They're meant as a guide to help clinicians at the bedside to begin to think about how best to treat their patients with acute hypoxemic respiratory failure or acute respiratory distress syndrome or ARDS.
Speaker: Yeah.
Speaker: And it's a starting point based on the available data and evidence that we have.
Speaker: And of course, there are still many gaps, still many questions left to answer, still challenges with guidance that can or can't be provided.
Speaker: So again, this is maybe a starting point and not necessarily the endpoint on how we might best treat our patients with ARDS.
Speaker: Perfect.
Speaker: And like many clinical guidelines and critical care today, obviously, the committee used a great methodology.
Speaker: And just if you could just maybe give us an overview at a high level, what is the difference for the final recommendations between a recommend versus suggest and the level of evidence for each one of those?
Speaker: Yeah, great.
Speaker: So like the idea here is to use a, you know, a methodological approach that helps us to synthesize the available data and from the synthesis of the data, then to generate clinical recommendations that form the guideline.
Speaker: And that's sort of the under the auspices of this grade methodology.
Speaker: And really, you get two main kinds of recommendations out of this, although in this guideline, I'm sure we'll talk a little bit about a third.
Speaker: You typically get strong recommendations or conditional recommendations.
Speaker: Strong recommendations are typically statements that you see in a guideline that state we recommend that you either do something or you don't do something.
Speaker: And conditional recommendations are worded as we suggest you do.
Speaker: do something or not do something.
Speaker: And again, so the idea is that for strong recommendations where we state we recommend, that pretty much means that the data tells us that almost in the absence of a contraindication, clinicians should always apply that recommendation in clinical practice, that the evidence is strong and sort of unambiguous and future data is unlikely to change our ideas about that recommendation.
Speaker: Conditional recommendations that are worded as we suggest
Speaker: are exactly that, that probably the majority of patients should have this intervention applied, but there might be some nuances in who and when to apply them, and future data may provide greater clarity
Speaker: on the intervention or therapy that we're talking about in that recommendation.
Speaker: And these are linked in some way to the level of evidence.
Speaker: So typically, not only do you get a strength of recommendation, but you also get a level of evidence, and that can be low, moderate, or high.
Speaker: And usually I guess that just comes into play to tell you how certain we are about the recommendation that we're making.
Speaker: And typically I would say perhaps for listeners is the idea that clearly the stronger the evidence, the more certain we could be about the recommendations that come from that.
Speaker: And it's a little bit unusual, but not impossible to typically have strong recommendations coming out of sort of low or very low levels of evidence as you might imagine.
Speaker: Perfect.
Speaker: One of the topics that was addressed in the guidelines that we're not going to discuss in detail today was definitions and phenotypes.
Speaker: Now, before we go into the respiratory support, which is really the focus of our conversation today, Eddie, could you just give us a practical view on ARDS definitions?
Speaker: You wear both a scientist and a clinician hat at different times.
Speaker: And obviously, there's always been a little bit of tension between defining ARDS at the bedside and in the clinical research.
Speaker: Yeah, I think this is maybe a somewhat unique feature of being critical care clinicians is that we have lots of syndromes and fewer diseases, ARDS and sepsis being chief amongst them.
Speaker: And as a result of these being syndromes, of course, we come up with definitions to make up what these clinical syndromes are.
Speaker: And of course, over the course of time, we modify or revise our definitions as more information becomes available.
Speaker: And Sergio, I think it's a good point that you make.
Speaker: I think for the point of view of research, we need rigorous definitions because that helps us to identify the populations that we're interested in studying, especially when we're thinking about epidemiology outcomes.
Speaker: We need to understand who's in and who's out.
Speaker: And also for clinical trials in terms of trying to think about as much as possible, defining homogeneous populations for study for particular therapies or interventions that we're interested in and having rigorous, valid and reliable definitions are very important.
Speaker: At the bedside, I would say we're probably a little bit less rigorous about this, and maybe I'll just speak for myself in saying I don't necessarily apply the Berlin definition as an example to every patient that I see at the bedside to really say they do or don't have ARDS.
Speaker: I think I think about that a little bit, especially when I'm, and today we'll talk about recommendations that apply to different severities of ARDS, but it's typically quite a bit more pragmatic at the bedside, right?
Speaker: If a patient's got severe,
Speaker: Respiratory failure in the setting of a known ARDS risk factor like pneumonia, aspiration, non-pulmonary sepsis, I pretty much label those patients at ARDS without necessarily going through all the motions of thinking about all the criteria from the Berlin definition, again, as an example.
Speaker: So certainly more stringent when I'm thinking with my scientific hat on and maybe a little less stringent when I'm thinking at the bedside with my clinician hat on.
Speaker: Perfect.
Speaker: And I think to some extent, Eddie, really what we're talking about within this syndrome is patients who have acute hypoxemic respiratory failure.
Speaker: Right.
Speaker: And those are the people we're treating and that it's a spectrum.
Speaker: And maybe if you apply the Berlin definitions quite early, they don't qualify.
Speaker: But 12 hours later, the next day they do.
Speaker: But like you said, as clinicians, we're interested in identifying people who need support.
Speaker: And what we're going to discuss today is the best way to provide that respiratory support.
Speaker: Yeah, 100% agree.
Speaker: And it's an interesting point in maybe a future podcast about how maybe the shift should be exactly that towards more broader definitions like acute hypoxemic respiratory failure, where we have fewer criteria to consider.
Speaker: Those are really the patients that we're
Speaker: thinking about at the bedside and more and more the data or the evidence tells us that these patients we should treat them the same as ARDS patients but I agree with you completely that's really what we're talking about today and I think the focus of many of the recommendations from the guidelines
Speaker: Perfect.
Speaker: Let's dive into some practical and tactical discussions here.
Speaker: So the first area I wanted to hear from you a little bit is high flow nasal oxygen and non-invasive ventilation in acute hypoxemic respiratory failure and ARDS.
Speaker: So why don't you tell us a little bit of the status right now of high flow nasal oxygen that obviously got a big push during COVID in many of our ICUs.
Speaker: And now there's some formal recommendations from the guidelines and also, I think, a body of literature that is trying to answer some of the questions of using this at the bedside.
Speaker: Yeah, so I think this is one of the nice features of this up-to-date guideline is that now we have a growing body of literature, as you mentioned, around the use of high-flow nasal oxygen and non-invasive ventilation.
Speaker: And certainly the pandemic brought this into sharper focus for many places around the world.
Speaker: And in fact, then we also now developed an evidence base around some of this.
Speaker: specifically in large populations of COVID-19 patients that were studied.
Speaker: On the other hand, I think as you'll see for readers of the guideline, this sort of introduces a bit of complexity specifically for this set of interventions, maybe less so for the other interventions we'll talk about later on the podcast, because there's
Speaker: a bunch of recommendations in this part that are sort of focused on COVID-19, and not all of them are the same or overlapping as those for patients who have acute hypoxemic respiratory failure, not from COVID-19.
Speaker: And again, this is perhaps the necessary evil of the methodologic or great approach is that when we have specific data generated in specific populations, it might make more sense to be specific about the recommendations, and maybe they don't
Speaker: apply as broadly as we might think, or at least to make those recommendations as broadly as we think.
Speaker: Although, again, I would say I'm definitely in the camp of people who, and I would say most of the people on the guideline panel that agree that, you know, ARDS that's developed from COVID-19 is ARDS.
Speaker: That's part of the, you know, etiologic agents or risk factors that lead to ARDS.
Speaker: So in the end game, we probably treat these patients the same.
Speaker: Nonetheless, for high-flow nasal oxygen, we considered patients that were not mechanically, invasively mechanically ventilated, that had IQ high-boxylamic respiratory failure that wasn't due to cardiogenic pulmonary edema or acute exacerbations of COPD.
Speaker: And again, what we found was that from the available data that we could recommend...
Speaker: So a strong recommendation that patients who were not receiving invasive mechanical ventilation with acute hypoxemic respiratory failure, again, not due to heart failure or acute exacerbations of COPD, could receive high flow nasal oxygen as compared to conventional oxygen therapy to reduce the risk of intubation.
Speaker: However, as many of the studies didn't show that that translated into a reduction in mortality, we couldn't make any specific recommendation for or against the use of high flow nasal oxygen as compared to conventional oxygen therapy to reduce mortality.
Speaker: And again, this is one situation where the recommendations were the same for patients with acute hypoxemic respiratory failure with or without COVID-19.
Speaker: And I think that the take-home message I take here is that even though some data suggests that it might prevent intubations, we have not been able to demonstrate the mortality benefit, but it seems that just based on that and the availability and other factors, we should be using it as a first step in many of our patients as we're evaluating them in the ICU.
Speaker: Would that be fair?
Speaker: Yeah, exactly.
Speaker: I think again, mortality is not the be all and end all of all things.
Speaker: And again, perhaps the pandemic brought this into sharp focus, like high flow nasal oxygen, it's pretty well tolerated by patients.
Speaker: It's less resource intensive than invasive mechanical ventilation.
Speaker: You could deploy it in areas outside of the ICU in certain settings.
Speaker: It might be related to fewer complications than if you're sedated with an endotracheal tube in place and that sort of thing.
Speaker: So even though, agreed, it doesn't reduce mortality, it might still have some good effects
Speaker: in using high-flow nasal oxygen.
Speaker: So I think agreed.
Speaker: I think this is one of the reasons why the recommendation came out as a strong one for this particular question.
Speaker: And from a practical perspective, I think that there's also updated guidelines on rapid sequence intubation suggesting that high-flow nasal oxygen is a good place to start.
Speaker: And these patients, if they're not going to get better, they're going to get intubated.
Speaker: So I think that, yeah, for sure, as a clinician, I have a...
Speaker: a low threshold to initiate high flow naso oxygen in these patients as I start evaluating them.
Speaker: Could you comment or contrast how does this apply to non-invasive ventilation and what we're meaning by here is bi-level positive pressure ventilation that's non-invasive?
Speaker: Yeah, so here again, I think is where this probably the most complex set of recommendations in the guideline, because there's quite a few comparisons to different modalities, whether you're talking about CPAP, non-invasive ventilation versus high flow nasal oxygen or conventional oxygen therapy, and then CPAP alone over conventional oxygen therapy.
Speaker: And then, of course, different interfaces like helmet and IV as compared to more traditional face mask and IV.
Speaker: So a bunch of recommendations here to consider.
Speaker: from the non-invasive ventilation point of view.
Speaker: And again, perhaps an explosion of specific recommendations here because a lot of these different modalities were specifically tested during COVID-19 in various populations.
Speaker: So maybe to start with a set of, a first set of recommendations that we can have some discussion is this idea of comparing
Speaker: CPAP or non-invasive ventilation to high flow nasal oxygen.
Speaker: So again, an important question that I think came up during the COVID-19 pandemic was non-invasive ventilation superior to high flow nasal oxygen.
Speaker: And again, the data at present at least doesn't seem to support that issue rigorously.
Speaker: And that's what led to this idea that we couldn't provide a specific recommendation for or against high flow nasal oxygen as compared to CPAP or non-invasive ventilation to reduce mortality
Speaker: or intubation in patients with acute hypoxemic respiratory failure that wasn't due to heart failure or acute exacerbations of COPD.
Speaker: Again, because we have good evidence that non-invasive ventilation is beneficial in those situations.
Speaker: We did, however, see that CPAP or non-invasive ventilation could be considered.
Speaker: So a suggest recommendation or a conditional recommendation could be considered instead of high-flow nasal oxygen,
Speaker: in patients who had acute hypoxic respiratory failure due to COVID-19 to reduce intubation, but again, no specific recommendation in terms of reducing mortality because the data there was less consistent.
Speaker: Perfect.
Speaker: And these are definitely changes from previous guidelines in terms that when I was in training, these were not even considerations for anybody who we labeled as ARDS, right?
Speaker: And I think that as we're learning how to support people, we are doing new tests and a lot of this came from need and COVID.
Speaker: But like you said, a lot of new data, but still a lot of unanswered questions.
Speaker: why don't we move Eddie to mechanical ventilation and maybe start with at least what I think in most clinicians is the least controversial of all, which is low tidal volume ventilation, but just tell us where we stand there today.
Speaker: Yeah, I think not surprisingly, um, this guideline consistent with previous, uh, guidelines in 2017 that we published for ATS, ESICM and SECM showing a very strong recommendation.
Speaker: And, um,
Speaker: and a high level of evidence supporting the use of low tidal volume ventilation strategies.
Speaker: So again, targeting 48 mils per kilo predicted body weight as compared to larger tidal volumes that are traditionally used to normalize blood gases, both to reduce mortality in these patients with ARDS, whether that's due to COVID-19 or not.
Speaker: So a general recommendation for ARDS of any etiology.
Speaker: And could you comment a little bit on plateau pressures?
Speaker: And that was not necessarily covered in detail in the guidelines, but obviously just from your clinician standpoint and scientist standpoint, what do you think is the appropriate target there and how we should manage that?
Speaker: Yeah, I think, again, here, the idea is that because, you know, some of the studies didn't necessarily have pressure limitation in addition to tidal volume limitation that wasn't specifically mentioned in this recommendation.
Speaker: But clearly, this recommendation is in large part driven by the landmark ERDS Network study showing that both targeting the lower tidal volumes and maintaining plateau airway pressure under 30 centimeters of water led to a very significant increase.
Speaker: Absolute risk reduction of nearly 9%.
Speaker: And so I think, yeah, clinically speaking, we would still suggest both reducing tidal volume and when possible limiting plateau airway pressure to less than 30 to derive sort of the big benefit that we saw in that ARDS network study.
Speaker: I think maybe a corollary to your question, Sergio, is the idea of sort of newer strategies like limiting driving pressure.
Speaker: I might just caution that although there's a strong physiologic rationale in a growing body of clinical data that supports the idea about limiting driving pressure as perhaps a better approach.
Speaker: way of thinking about lung protection that both incorporates lung compliance and tidal volumes or scaling tidal volume to respiratory system compliance.
Speaker: We don't yet have large randomized control trials demonstrating a benefit of primarily targeting driving pressure as compared to tidal volumes or plateau error pressures.
Speaker: That's why you don't see a recommendation specifically in this guideline.
Speaker: I would say any guidelines I'm currently aware of about limiting driving pressure, although trials are ongoing that will hopefully help to clarify that.
Speaker: question in the future for sure and i think that as intensivists we always like the new shiny toys right and the new shiny ideas and even when the physiological basis is sound and we have been fooled before right by thinking that we understood the physiology and then we do a trial and it is harmful so i i agree i think focusing on
Speaker: The best available evidence supported strategies first and foremost is really key.
Speaker: And that's where the low tidal volume and targeting the plateau pressures, like you said, of 30 or below centimeters of water is really the way to go.
Speaker: What about PEEP?
Speaker: Yeah, so PEEP, not surprisingly, something I'm sure we've been talking about for 40 years, we'll talk about for another 40 years.
Speaker: And here, again, using the GRADE methodology by synthesizing the available trials, we couldn't come up with a specific recommendation for or against the use of higher versus lower PEEP titration to reduce mortality in ARDS.
Speaker: that that recommendation was also the same, whether that was ARDS from or not from, not due to COVID-19.
Speaker: Again, because the clinical trials show equivocal results, as many listeners will be aware of.
Speaker: And unfortunately, I think, again, similarly, as more recent trials sort of trying to find ways to individualize PEEP titration, looking for a benefit there that perhaps using physiologic measurements or
Speaker: PEEP titration guided by respiratory mechanics might lead to a more personalized setting of mechanical ventilation.
Speaker: We also, again, because of the available data, could not provide a specific recommendation for or against the use of PEEP titration guided by respiratory mechanics versus the PEEP-FIO2 table to reduce mortality in ARDS.
Speaker: So really no strong, no recommendations one way or the other about higher versus lower PEEP and the best strategy to titrate PEEP in these patients.
Speaker: Now, in terms of clinical behavior at the bedside, like you said, physiologically and from what we understand of event of the induced lung injury, there is obviously an apparent benefit to having PEEP and preventing the recruitment and recruitment of alveoli on a regular basis.
Speaker: How do you set PEEP, Eddie, at the bedside?
Speaker: Yeah, I think, you know, again, I agree.
Speaker: I think as the lung, as the lung injury is more severe, it makes sense that to me, at least that higher levels of PEEP are typically required.
Speaker: And again, I mean, much like it's codified here and then no specific recommendation for or against using these physiologic PEEP titration strategies, I like to start and use the PEEP-F-O2 table.
Speaker: So my ICU, the standard way of setting PEEP,
Speaker: is to use the PEEP-FIO2 table.
Speaker: And in fact, we have some studies, including one from Davida Cumelo, showing exactly that the most reliable method of setting higher levels of PEEP in sicker lungs was the PEEP-FIO2 table when you compare that to the stress index, esophageal manometry, or the titration method used in the EXPRESS trial.
Speaker: So we start with the PEEP-FIO2 table.
Speaker: And I would say when we don't see results that we expect, or we have challenging patients, perhaps a patient who has
Speaker: chest abdominal wall, complex thoracic or abdominal surgery or trauma, very obese patients where we might be fooled by the PEEP-FIO2 table, that's when we might go the second step of employing strategies at the bedside like esophageal manometry, electrical impedance, tomography, those sorts of things to fine tune our PEEP setting.
Speaker: But our starting point is always the PEEP-FIO2 table.
Speaker: Perfect.
Speaker: What about recruitment maneuvers?
Speaker: Yeah, recruitment maneuvers have come full circle, I would say.
Speaker: Like in our original 2017 guideline, we actually had a conditional recommendation for recruitment maneuvers because, again, the data up to that point had sort of consistently shown that recruitment maneuvers could lead to an improvement in oxygenation, albeit transient in some situations.
Speaker: But since then, I think increasing amounts of data have suggested now that
Speaker: recruitment maneuvers are probably not as useful as we think.
Speaker: And certainly some of these more prolonged high pressure recruitment maneuvers, such as those tested in the alveolar recruitment study could actually lead to harm.
Speaker: And so based, you know, in large part due to the results of that alveolar recruitment trial, there's a strong recommendation against the use of prolonged high pressure recruitment maneuvers to reduce mortality in patients with ARDS.
Speaker: Again, that's with or without COVID-19.
Speaker: And conditional or suggest recommendation against the routine use of brief, even the brief high pressure recruitment maneuvers to reduce mortality in ARDS.
Speaker: Again, because the synthesis of the evidence now suggests, again, more harms than benefits from the use of these either prolonged or brief high pressure recruitment maneuvers.
Speaker: And just to remind the listeners, prolonged is more than one minute, brief is less than one minute, and high is above 30, 35 centimeters of water.
Speaker: Is that correct?
Speaker: Correct.
Speaker: That is correct.
Speaker: It's interesting, Eddie, how recruitment maneuvers were something that a lot of us were doing at the bedside frequently before the studies.
Speaker: It reminds me also of, I mean, a lot of the enthusiasm that many intensivists had for high frequency oscillator ventilation and how when we do studies, all of a sudden we find that they actually can be harmful if not, it does not work.
Speaker: So I think it's just a good reminder of not physiology doesn't always give us the answers and that we should always operate within the best available evidence.
Speaker: Are there additional clinical pearls that are not covered in the clinical guidelines regarding like the basic mechanical ventilation that you want to emphasize?
Speaker: So this is what I think is everybody who gets intubated should get.
Speaker: And it's like the first three steps of caring for these patients.
Speaker: Yeah, I think that, you know, again, the guideline document is pretty robust and it comes with a big supplement with a lot of details.
Speaker: But I think agreed, like I think thinking to myself what I think at the bedside and, you know, to my colleagues who are reading the guideline, I think, again, I love to keep things simple.
Speaker: So for me to distill the guideline down, it's really that.
Speaker: Lung protective ventilation, so low tidal volume, pressure limited ventilation really should apply for all.
Speaker: To me, that's the standard of care in providing invasive mechanical ventilation to patients with acute hypoxemic respiratory failure.
Speaker: And then keeping things simple is that then we set PEEP using the PEEP-FIO2 table as a starting point.
Speaker: you know, sort of keeping it simple is key.
Speaker: And so if we sort of start with six mils per kilo predicted body weight, you know, most all patients in the absence of, you know, some special considerations and set PEEP using the PEEP-FL2 table, to me, that's what the guideline is really trying to tell you.
Speaker: I don't know that we need any other fancy strategies that suggest like, you know, physiologic measurements or that sort of thing in the vast majority of patients.
Speaker: And if we stick to those
Speaker: tenants, then again, I think we're really applying the best evidence-based medicine we can for most of these patients with acute hypoxemic respiratory failure.
Speaker: Perfect.
Speaker: So we institute all these evidence-based settings in our lung protective mechanical ventilation, and we're still having trouble with the patient.
Speaker: A lot of people would argue, okay, next step would be to consider prone positioning.
Speaker: So could you tell us a little bit about a current state of prone positioning in mechanically ventilated patients?
Speaker: Yeah, so I think again, you know, based in large part from the results of the Proceva study, there's been a clear paradigm shift regarding the use of prone positioning.
Speaker: And again, perhaps the silver lining of the pandemic has been the increasing uptake of prone positioning in patients with moderate to severe ARDS.
Speaker: So consistent with the recommendation that was made in 2017,
Speaker: We have a strong recommendation for the use of prone positioning and moderate to severe ARDS and that's patients with a PF ratio less than 150 to reduce mortality and that was again a recommendation that is the same for patients who have COVID-19 or don't have COVID-19 associated ARDS.
Speaker: And the key thing, again, from Proceva and the evolution of clinical trials about prone positioning over the last few decades is that starting earlier is better.
Speaker: And so there, again, is a strong recommendation that starting prone positioning early in patients with ARDS after they're stabilized on invasive mechanical ventilation and keeping them in the prone position for prolonged periods, which we defined as more than 16 hours,
Speaker: is recommended to reduce mortality in these patients.
Speaker: And again, that recommendation is the same for patients who have ARDS from COVID or patients who have ARDS from an etiology other than COVID.
Speaker: So a very important adjunctive measure in patients, as you mentioned, who don't stabilize with the measures that we spoke about previously.
Speaker: And I think an important point to emphasize and highlight is that the guidelines have a recommendation on the timing.
Speaker: And like you said, this is a time-sensitive intervention, and we should be doing it earlier rather than later.
Speaker: And I think it's important because I often have seen teams think of ECMO or think of other therapies that might be less
Speaker: But they haven't really gone through the first couple of steps that the evidence would suggest.
Speaker: And that includes proning, for example.
Speaker: Yeah, I think I think and maybe the surgery, I completely agree with you.
Speaker: And I think maybe part of the important message for listeners, again, is that is to discard this idea that prone positioning use ECMO as an example, that prone positioning is some kind of rescue intervention or salvage intervention.
Speaker: Prone positioning is a lung protection maneuver.
Speaker: And that's why doing it early, just like instituting low tidal volume ventilation.
Speaker: is important is because it's a lung protection maneuver.
Speaker: We don't wait until the patient worsens.
Speaker: It's not an oxygenation rescue maneuver.
Speaker: We basically institute it early in patients who meet the criteria.
Speaker: So moderate to severe RDS with PF ratio less than 150, because the benefit is, is, um,
Speaker: is mediated through enhancing the homogeneity of ventilator distribution.
Speaker: It reduces, we think, therefore, ventilator-induced lung injury, and that's the benefit, lung protection.
Speaker: So we don't wait until the patient worsens or reaches some critical threshold.
Speaker: We want to do it early because it protects the lung.
Speaker: In terms of practical application of the proning maneuver or proning patients, you did mention that following, obviously, Prasiva, it's usually 16 hours of prone position, and then you put them supine and reevaluate.
Speaker: How many sessions do you do, or when do you stop proning the patient, Eddie, in your practice?
Speaker: Yeah, so, you know, in the Proceva study, on average, patients were randomized.
Speaker: The proning group received about four and a half proning sessions.
Speaker: So that's about four and a half days of proning.
Speaker: And in the Proceva study, they had certain criteria to terminate proning, which essentially was an improvement in hypoxemia, amongst some other things.
Speaker: So we use, I would say, very similar results,
Speaker: similar criteria, excuse me, in our practice of prone positioning where once patients, when they're returned to the supine position and they're durably maintaining their PF ratio above 150 or 200, 200 was used in the Proceva study, then we would stop proning them.
Speaker: During the supine positioning portion, if their PF ratio remained below 150 for some part of the day, we would continue to prone them until they were durably above 150.
Speaker: And that's the criteria we've been using in our clinical practice.
Speaker: Do you interrupt proning for any particular complications?
Speaker: Not particularly.
Speaker: We probably, one of the reasons we might interrupt prone positioning is to facilitate diagnostic or therapeutic intervention.
Speaker: So for instance, if the patient has to go because we need it, like for a CAT scan or needs an echo,
Speaker: needs bronchoscopy or something like that, that's probably one of the main reasons we might interrupt proning for that point of view.
Speaker: But in the prone position, if there isn't any specific complications, and it's hard to think of any, like, I mean, there might be endotracheal tube dislodgement or obstruction.
Speaker: There could be worsening in some cases, hemodynamic instability, but absent those things, we wouldn't typically interrupt prone positioning.
Speaker: And final question on the proning, Eddie, what if there's no response at all in the oxygenation?
Speaker: Yeah, so this is another critical fact.
Speaker: So, you know, we now have pretty good data in a secondary analysis of Proceva led by Rich Kelly showing that oxygenation response is a poor surrogate for proning response.
Speaker: So the key is that in this secondary analysis, patients who did or didn't have an oxygenation response to proning both derived a mortality benefit from
Speaker: from proning.
Speaker: And this is no different than what we saw in the ARMA trial, the ARDS network trial, right?
Speaker: So patients randomized the low tidal volume group, had worse oxygenation on day one, but they ultimately derived the 9% reduction in death
Speaker: from being randomized to the lung protection group.
Speaker: So oxygenation, remember, is unfortunately a poor surrogate for mortality in patients with ARDS.
Speaker: And here, we also don't want to necessarily use the oxygenation response to determine a quote-unquote response to prone positioning.
Speaker: This is not an oxygenation maneuver.
Speaker: This is a lung protection maneuver.
Speaker: So as long as the patient doesn't develop, as you asked before, Sergio, a life-threatening complication from prone positioning, I would keep them in the prone position irrespective
Speaker: of what the oxygenation response or non-response is.
Speaker: And I think it's important, right?
Speaker: Because if somebody's oxygen gets worse, we're not going to increase the tidal volume, right?
Speaker: That's not the response.
Speaker: We're trying to protect the lungs.
Speaker: So I think it's an important point, like you said, that we now better understand after the secondary analysis of placebo.
Speaker: So thanks for covering that.
Speaker: No problem.
Speaker: What about...
Speaker: non-intubated patients, so the awake prone positioning that became, I think, almost more of treating the clinicians during the COVID surges.
Speaker: But obviously we've learned something.
Speaker: And what is the recommendation these days?
Speaker: Yeah, so the main recommendation here, as you mentioned, this is really a phenomenon, I think, that became more readily used in the pandemic and then studied as a result.
Speaker: It really was more of a niche area prior to the pandemic.
Speaker: So this led to a recommendation specifically for non-intubated patients with COVID-19 associated acute hypoxic, systemic respiratory failure that you could, we suggest, using awake-prone positioning for these patients to reduce the risk of intubation.
Speaker: but it didn't seem no recommendation to use awake-prone positioning in patients with COVID-19 associated acute hypoxemic respiratory failure to reduce mortality.
Speaker: And similarly, no recommendation for or against awake-prone positioning for non-intubated patients with acute hypoxemic respiratory failure, not due to COVID-19, again, because of the paucity of data prior to the pandemic.
Speaker: So really, again, based on a few studies now that showed that awake-prone positioning seemed to
Speaker: reduce the risk of intubation in these patients with COVID-19, but that, again, didn't translate into a reduction in mortality.
Speaker: Perfect.
Speaker: Let's move on to another topic.
Speaker: And now we are going more into the realm of things that would be applied to some patients who are not responding to the first couple of steps that we discussed and mentioned.
Speaker: Neuromuscular blockers, and there's been obviously some changes in the evidence, but also I think there was, I would say, a significant increase in their utilization during COVID-19.
Speaker: for many reasons, I'm sure.
Speaker: But where do we stand today?
Speaker: And maybe here we have to separate non-COVID from COVID patients.
Speaker: Yeah, so I think, again, the bulk of the data that informed this recommendation came in ARDS patients studied before COVID.
Speaker: So maybe to jump ahead in that, there were no specific randomized controlled trials or data looking at COVID-19 ARDS patients.
Speaker: So we were unable to make a recommendation for or against the routine use of ARDS.
Speaker: neuromuscular blockade in patients with moderate to severe COVID-19 associated ARDS because we can only have indirect evidence and no direct evidence in those populations.
Speaker: But looking at trials that happened before the pandemic, specifically Acurisys and ROSE, the group made a recommendation against the routine use of continuous infusions of neuromuscular blockade to reduce mortality in patients with moderate to severe ARDS.
Speaker: And what do you feel in terms of COVID patients?
Speaker: Would you use neuromuscular blockers, if so, for how long and when?
Speaker: Yeah, I think these are important questions to answer.
Speaker: And in fact, you know, I would urge listeners to consider reading our update to the ATS guidelines for ARDS, which was just published this month.
Speaker: In January 2023, because we actually made a slightly different recommendation for neuromuscular blockers because the evidence synthesis in both guidelines was the same.
Speaker: The point estimate for mortality was actually in favor of neuromuscular blockades, although the confidence intervals were wide and included one.
Speaker: So that led to this idea that, and there are, you know, potential complications related to the use of continuous infusions of neuromuscular blockade, as we know about.
Speaker: Chief amongst the concerns would be things like ICU-required weakness and complications such as that, neuromuscular complications.
Speaker: But again, you know, there were trials that showed a benefit perhaps in preventing ventilator-induced lung injury, specifically in our curis, as a very significant reduction in the risk of pneumothoraces.
Speaker: So again, I think on the balance of things, in our practice, we used a lot of neuromuscular blockade in these COVID-19 patients because we thought they were very high risk, some of them for ventilator-induced lung injury.
Speaker: But your questions are a good one in terms of how early should we institute them?
Speaker: Is cis-atricurium, which is the neuromuscular blockade agent that was studying these trials, necessary?
Speaker: Or is it a class effect that extends to other
Speaker: neuromuscular blocking agents and for how long should we continue if we start it in these patients?
Speaker: Again, in the trials, 48 hours was the use, although in the clinical practice, it sometimes was quite a bit longer, in particular for COVID patients.
Speaker: I think these are questions that we still need to answer.
Speaker: There's been a number of secondary analyses in observational studies that have sort of suggested
Speaker: Perhaps there were in some populations, there could be benefits to extending infusions of neuromuscular blockade.
Speaker: But again, those are hypothesis generating.
Speaker: And hopefully this recommendation, along with the one that we put forth in the ATS guideline, will help stimulate a future study that might help provide better clarity on the role of neuromuscular blockers in patients with ARDS.
Speaker: Perfect.
Speaker: And now I would like to maybe go into the world of ECMO.
Speaker: I mean, obviously a world that you're very invested in.
Speaker: And what's the current recommendation of the guidelines regarding the use of ECMO for ARDS patients?
Speaker: Yeah.
Speaker: So in the 2017 guideline, listeners might recall that at the time EOLIA wasn't published, we had CSER as the only modern adult trial.
Speaker: So we didn't have sufficient evidence based on just one trial.
Speaker: that had some methodological issues to contend with to make a recommendation for against the use of ECMO for ARDS.
Speaker: But now with the publication of Eolia and the totality of the literature, in this guideline, we were able to recommend that in severe ARDS patients,
Speaker: as defined by the EOLIA inclusion criteria, that they should be treated with ECMO in an experienced ECMO center using a management strategy that was very similar to that that was employed in the EOLIA trial.
Speaker: And this recommendation also applied to severe ARDS from COVID-19, just as it did for patients with severe ARDS without COVID-19.
Speaker: And in terms of, I think, worth a little bit more discussion, Eddie, is a lot of centers, a lot of listeners probably don't have ECMO capability, right?
Speaker: So the idea is, what are the things you need to implement and when should you identify a patient to be referred to an ECMO center?
Speaker: And I'm sure that in Canada, that is the same way.
Speaker: There are centers that do ECMO more regionalized and then there are centers who have to refer those patients.
Speaker: Could you comment on terms of
Speaker: what would be the proper timing, how we should be thinking about this, and maybe review some of the criteria from Aeolia?
Speaker: Yeah, so I think, again, the key thing here is agreed.
Speaker: Like, I don't think every hospital needs to provide ECMO.
Speaker: It could be more of a regionalized resource, again, because it is quite costly, resource intensive.
Speaker: It requires a large team of supporting clinicians to best manage these patients.
Speaker: So I think for centers that don't have ECMO capability, I think the key things here would be to create links, referral links with centers that could provide it in the event that you do need to refer patients so you could build that relationship.
Speaker: And I think the key is that in building that relationship with the ECMO referral center is the idea that clinicians and non-ECMO centers feel comfortable calling those referral centers early.
Speaker: Again, and I would say, at least in my practice, there's no hard and fast rules about what triggers a consult, but the idea is typically the same.
Speaker: It's clinical intuition that something about the patient is not moving in the right direction.
Speaker: Now, some of these patients will get bad very quickly.
Speaker: We saw a lot of that in COVID.
Speaker: So you might call very early, hours after they hit the emergency department.
Speaker: They're getting very hypoxemic and progressing through the gamut of interventions that we've already talked about in the guideline.
Speaker: And then you want to call about ECMO.
Speaker: And then others, of course, worsen more slowly.
Speaker: And then you might...
Speaker: pick up the phone on day three, four or five because things are worsening despite
Speaker: sedation, neuromuscular blockade, prone positioning, and these sorts of things, and ask for an ECMO referral.
Speaker: But again, the idea is to feel comfortable calling at any point to get that opinion and that discussion going with your ECMO referral center.
Speaker: Sort of the criteria that were outlined in the EOLIA trial for ECMO are the ones that we also use at our hospital.
Speaker: So there was a fast hypoxemia criteria and a slow hypoxemia criteria.
Speaker: So the fast one was a PF ratio of less than 50.
Speaker: for more than three hours.
Speaker: Or for the slower hypoxemia criteria, there's a PF ratio of less than 80 for more than six hours.
Speaker: So generally, we sort of say if your PF ratio is less than 80 for any period of time, again, you might not wait the whole six hours to make the call.
Speaker: Once you see it dipping below that, you might want to alert your local ECMO center to say, you know, I'm worried about this patient.
Speaker: His severity of lung injury and hypoxemia is worsening.
Speaker: Would you consider this patient for ECMO?
Speaker: And there was also a hypercapnia
Speaker: That criteria with a pH less than 7.25 with the PaCO2 greater than 60 for more than six hours.
Speaker: That also could lead to consideration for despite optimal mechanical ventilation and a trial of prone positioning in the absence of contraindications.
Speaker: That might also be a patient who's a candidate for ECMO.
Speaker: Perfect.
Speaker: And I know that in the extracorporeal life support section of the guidelines, there was also a very strong recommendation, high level evidence against the use of extracorporeal carbon dioxide removal or ECCO2, I guess, which I have never really utilized.
Speaker: But could you just comment on that a little bit?
Speaker: Yeah, there's a lot of interest, as you mentioned earlier in the podcast, Sergio, about the new shiny toy.
Speaker: So this is a new modality.
Speaker: It's a lower flow extracorporeal support that mainly functions to remove CO2 rather than provide oxygenation.
Speaker: To provide oxygenation, you need higher levels of blood flow, higher degrees of support of cardiac output.
Speaker: But here with lower flow,
Speaker: it's more of a intervention to remove CO2.
Speaker: And the idea here is that we felt there'd be a lot of promise in using this kind of a system to remove CO2 to facilitate even more lung protective mechanical ventilation.
Speaker: So if we lower the intensity of mechanical ventilation further, just an example, if you lower tidal volume further, below four mils per kilo, you're going to get hypercapnia.
Speaker: And so
Speaker: The idea here is to remove the CO2 extracorporeally so you could facilitate that reduction in mechanical ventilation intensity further.
Speaker: We think that might lead to more lung protection and more lung protection might lead to better outcomes for patients.
Speaker: This recommendation in large part was fueled by, unfortunately, a study led by Danny McCauley and James McNamee in the UK called the REST trial,
Speaker: which tested this hypothesis in patients with acute hypoxemic respiratory failure.
Speaker: And again, as you've mentioned time and time again on this podcast, Sergio, although we thought it was going to be a good idea, it not only wasn't beneficial for patients with ARDS, it actually led to harm.
Speaker: There was an excess number of intracranial hemorrhages and bleeding complications, fewer ventilator-free days.
Speaker: Although there was no significant difference in mortality, mortality was in the wrong direction for extracorporeal CO2 removal.
Speaker: So the results of that trial, in large part, fueled this strong recommendation against the routine use of extracorporeal CO2 removal in patients with ARDS.
Speaker: And I think, Eddie, it's interesting, right?
Speaker: It's always a reminder that we have an enormous talent to convince ourselves of what we want to think, right?
Speaker: So the confirmation bias.
Speaker: And we can come up with all sorts of great explanations of why something might work and why we should do it.
Speaker: Yet at the end of the day, the scientific method is the only way forward.
Speaker: And you have to...
Speaker: empirically test, right?
Speaker: And you have to have a falsifiable hypothesis, like in this case.
Speaker: And that's how we, I think we really advance our knowledge.
Speaker: Yeah, I think that's absolutely true.
Speaker: And again, I think a lot of that is based on the costs of the things that we do.
Speaker: I think, you know, sometimes we feel like there's a great tension in critical care between the idea of physiologic principles or physiology guided treatment and
Speaker: And evidence-based medicine.
Speaker: And I've certainly participated in my fair share of debates on this issue.
Speaker: But again, they're really complementary.
Speaker: And this is really not a criticism of the underlying physiology.
Speaker: I think the physiological principles of, for instance, lung recruitment or an open lung or reducing the intensity of mechanical ventilation in this situation, as an example, these are strong and good physiologic concepts.
Speaker: The challenge is, of course, is that in 2024, the only way we could facilitate lung recruitment or CO2 removal is using some kind of imperfect intervention.
Speaker: If we had some intervention that had very few risks, I think achieving those goals would be very good.
Speaker: The physiology is not lying to us.
Speaker: But of course, in the real world, what we have is we have certain interventions to accomplish those goals.
Speaker: And unfortunately, at the present time, those interventions have more risks than benefits.
Speaker: So these ideas are complementary.
Speaker: It's not a criticism of the physiologic concepts or principles.
Speaker: It's just that we have imperfect tools to
Speaker: And of course, we're working hard to find better tools where the risk benefit ratio is far in favor of benefits and risks.
Speaker: Excellent.
Speaker: As we close and we try to put it all together from a very practical perspective, what is Eddie's, Eddie Fan's approach or summary of ARDS?
Speaker: Yeah, I think it's very simple as I hope I've told the group like it is what I do at the bedside.
Speaker: It's low tidal volume ventilation, low tidal volume ventilation, low tidal volume ventilation for all patients who are invasively mechanically ventilated in my ICU.
Speaker: We set PEEP using the PEEP-FIO2 table.
Speaker: Very simple.
Speaker: and only customize when we run into trouble or in patient populations that we know could be challenging.
Speaker: Again, as I mentioned, patients with complex thoracic abdominal surgery, as an example, morbid obesity might be another group that we might consider customizing or using additional tools.
Speaker: And then from there, if patients worsen, I sort of follow the gamut of the recommendations that we've had here.
Speaker: We institute deep sedation and probably neuromuscular blockade in my ICU.
Speaker: That leads again early to a trial of prone positioning in the absence of contraindications.
Speaker: And when patients fail that basket of interventions and meet Eolia criteria for ECMO and they don't have contraindications, then we would put those patients back.
Speaker: onto ECMO.
Speaker: So I think to us, and again, some patients might pass through the entire spectrum of those interventions quickly if they're very sick, and others might progress through that, if at all, over the course of days.
Speaker: And of course, it's just keeping a very close eye on these patients while they're in your intensive care unit, and then applying these strategies, again, at least in my ICU, in that order typically.
Speaker: Perfect.
Speaker: Eddie, what are you most excited about regarding upcoming trials or future research in ARDS?
Speaker: Yeah, I think, you know, that maybe two things, one, one, a very exciting that sort of addressed at the beginning of this guideline that you touched on a little bit, Sergio, is the idea of, you know, you know, our idea of our burgeoning understanding of, you know, phenotypes or sub phenotypes in the RDS that might lead to, you know, more identifying subgroups of patients who would more benefit from certain interventions, others that would less benefit and sort of a
Speaker: a way or a window into the idea, the holy grail of personalizing or individualizing the care of ARDS patients.
Speaker: I think as we learn more and more from many pioneers in this field and that some of that ability to identify these patient subgroups at the bedside is becoming more and more within reach that maybe, you know, the next time we have a podcast about this, we'll be talking about ways to
Speaker: personalized medicine for these patients rather than applying blanket recommendations that apply, we think, to large swaths.
Speaker: of ARDS patients.
Speaker: So I'm pretty excited about that kind of research and I apologize for maybe a self-serving excitement, but we are very excited about this idea of driving pressure and whether a ventilatory strategy in ARDS patients that's focused on limiting driving pressure would again, lead to increased benefits rather than focusing on tidal volume or plateau airway pressure alone.
Speaker: And so myself and my colleagues, Ewan Golliger, Neil Ferguson,
Speaker: And Serena Sahetia at Johns Hopkins are leading an international trial called the DRIVE trial, which is looking to randomize up to 4,000 patients to understand whether limiting driving pressure in these patients will be of benefit.
Speaker: Excellent.
Speaker: And we'll be definitely awaiting for more data and results and maybe talking about those two, I think, indeed, very exciting areas of ARDS treatment.
Speaker: Eddie, we like to close the podcast with a couple of questions that are unrelated to the clinical topic.
Speaker: Would that be okay?
Speaker: Absolutely.
Speaker: So is there a book or books that have influenced you significantly or that you have gifted often to other people?
Speaker: I'm not sure if I've gifted because they typically come back to me.
Speaker: My favorite author of the English language is James Joyce.
Speaker: And when I was a high school student, I read my first James Joyce book, which was a portrait of the artist as a young man.
Speaker: So it's not even anything about medicine, but really revolutionized my thinking about, um,
Speaker: thinking about life in this book, which is a semi-autobiographical book about James Joyce, but really his ideas about art, philosophy, and life.
Speaker: That book really changed my way about thinking about these things and really, I would say, ignited my love of reading fiction and philosophy and that sort of thing.
Speaker: So that was probably one of the most influential books and certainly the most influential author that I've read in my life.
Speaker: Perfect.
Speaker: And we'll definitely put links in the show notes.
Speaker: Is there something you believe to be true in medicine or life that other people don't believe or don't act like they believe?
Speaker: Well, I'm not sure that I know anything more than most people and probably much less.
Speaker: But I think certainly as my career has progressed, I certainly have bought into this idea that that's true in medicine and probably true in life is that less is more.
Speaker: I think, especially in the critical care unit, I think we're finding that, again, all the things that we do to patients have important either short-term or long-term consequences.
Speaker: And the less that we do and the more that we allow patients to take their own course and have time to heal their lungs, their kidneys, their hearts, and this sort of thing, that's really the way to go.
Speaker: And so I'm not sure that most people don't believe that, but I think certainly in our field, this idea that less is more is becoming more and more entrenched
Speaker: And I want to give a shout out to one of my colleagues at the Cleveland Clinic, Matt Suba, who has this line I love.
Speaker: He's written a lot about the Zentensivist and this sort of thing.
Speaker: But the idea that the intensive care unit is about maximal attentiveness and minimal invasiveness, which I think, again, encapsulates this idea of less is more quite beautifully.
Speaker: Perfect.
Speaker: And lastly, Eddie, is there anything you want every listener to know?
Speaker: Could be a quote, a fact or just a parting thought.
Speaker: Yeah, I think, again, the pandemic has taught us a lot about being humble about what we know and what we don't know, and especially in the light of a great unknown.
Speaker: And Sergio, you've already touched on this many times.
Speaker: I love this quote.
Speaker: Maybe it's paraphrased from Winston Churchill is that when the facts change, I can change my mind.
Speaker: And that's what it is.
Speaker: We might have strong held beliefs and we start out by trying to investigate and study and understand.
Speaker: And of course, that's OK to have start off with a strong belief.
Speaker: But
Speaker: When the facts change, when the data comes in and the evidence tells us what the answer is, then we have to be flexible and humble and change our thinking about things based on the prevailing evidence.
Speaker: Perfect.
Speaker: Eddie, thank you so much for sharing your expertise and your time with our audience.
Speaker: Always a pleasure to talk with you.
Speaker: Best of luck with the DRIVE trial.
Speaker: And we definitely want to have you back to hear more about phenotyping and driving pressures in the future.
Speaker: That's great.
Speaker: Thank you so much for the kind invitation and really a pleasure always to speak with you and to participate in the podcast.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sounds transforming the way critical care is provided in hospitals across the country.
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