Morning everyone, my name is Yasir Javed and I'm gonna be introducing everyone. So our session is on advanced ventilator management, where technology meets physiology. So in the next four talks, we'll be exploring a lot of physiological principles and their interface with technology and how some of the stuff is used at bedside, some of the stuff is being introduced at bedside. So I'm hoping after all these talks, you guys can take some of these physiological principles and apply them in your practice. So allow me to introduce Dr. Nidha Kardar. She's gonna be talking about PEEP and tidal volume titration. Thank you. Thanks, good morning everybody. Thanks for coming to a 715 session. I have no disclosures. I'm gonna start by pontificating on what we do in critical care, which 99% of it was what I consider supportive care. We're providing life support while giving time for healing and supportive care. It sounds like this really nice term, right? Like it makes me think of a hog and chicken soup, but as we all know it, it actually looks like this. So while we are providing supportive care, we are working pretty hard to minimize the damage caused by that supportive care. So that's gonna be a theme of what I'm gonna be talking about next. So when that comes to the ventilator, our goals, of course, are to support gas exchange and minimize adverse effects while we're supporting gas exchange. And with that in mind, get the patient off of the ventilator as soon as possible. So how does that relate to PEEP and tidal volume? They, of course, both support gas exchange, but in terms of adverse effects, from a pulmonary standpoint, you have too much tidal volume or too much PEEP that leads to overdistension, which leads to increased lung stress, lung strain, and increased dead space. Too little, you get atelectasis and inadequate gas exchange. So in turn, there are hemodynamic effects of that. So both atelectasis and overdistension can directly increase PVR through mass effect on the intraalveolar vessels. And then with inadequate gas exchange can lead to further pulmonary vasoconstriction, which further increases PVR. Too much PEEP or tidal volume can also, of course, increase intrathoracic pressure, which decreases RV preload. So I wanted to touch on a few terms and equations. So I mentioned stress, strain, and dead space. So stress, from a biomechanics standpoint, is defined as force per unit area experienced by an object, by an outside force. So your clinical correlate, when it comes to the lungs, is gonna be your transpulmonary pressure, your plateau pressure minus your pleural pressure, which if you have esophageal monitors, your esophageal pressure will be your surrogate there. On a simpler level, think of your driving pressure. This is something we all have access to for caring for patients on ventilators. So your plateau pressure minus your PEEP. Lung strain is then the resultant amount of distortion experienced by an object compared to its original dimension. So clinical correlate there is your tidal volume minus your FRC. Or again, at the bedside, more simplified, just think about your tidal volume. Alveolar dead space fraction is the fraction of your tidal volume that does not participate in gas exchange. So your PCO2 minus your end tidal CO2 over your PCO2 is one way to calculate it. Your end tidal CO2 over your CO2 is another surrogate that can be used as reflective of the dead space. So another issue we have is that the lung, by the time we're seeing them, it's never really homogenous, right? So this is a pretty extreme example where you have very dense consolidation in the right lung and fairly well aerated left lung. So what happens when we ventilate patients like this? Well, we're ventilating the entire system. We're not ventilating each lung individually, right? So your right side alveoli start out collapsed. Your left-sided alveoli are well aerated. You apply PEEP or increase your PEEP, and what happens? So your left-sided alveoli can become over distended, and with the over distension, your intra-alveolar vessels can become compressed. So with that, gas exchange worsens. You get increased dead space. On the flip side, on the right side, those right-sided alveoli, they may expand minimally or even not at all and remain collapsed, and because you have compressed your intra-alveolar vessels on the left, some of them may shunt back to the right side, and that's in spite of the hypoxic vasoconstriction that was originally happening there. So overall, what happens? You get increased lung stress and strain, increased dead space, and impaired gas exchange. And so that chest X-ray is an extreme example, but you're gonna see this in homogeneity in more uniform lung processes as well. The lung is never gonna be homogenous by the time patients are presenting to us in the ICU. Hemodynamic consequences, so again, I mentioned increased RV afterload, decreased RV preload, pulmonary vasoconstriction. So resulting from that, you get RV dysfunction and shock, just to add to the fun. So how do we minimize these adverse effects? So we have hopefully all learned about lung protective ventilation at this point, something we've known about for over 20 years, so keeping your tidal volumes under six mL per kilo predicted body weight, plateau pressure less than 30. You also want to take steps to limit lung inhomogeneity. So prone positioning is one of those things. Optimizing PEEP is gonna be another one of those things, which I'll get into. So can we do more than this? And gonna talk up next about a few principles that I think can help us do more. So driving pressure, I touched on earlier, correlates with lung stress. Again, it's plateau pressure minus PEEP, or your tidal volume over your static compliance. So caveats to driving pressure, being reflective of lung stress, is that this is dependent on your entire respiratory system, including your chest wall. So if there is abnormal chest wall compliance in, say, a very obese patient, this is not gonna be fully reflective of lung stress. However, it is an independent predictor of ARDS mortality. So tidal volume and PEEP changes actually only improve survival if they result in a decrease in driving pressure. What is the safe upper limit? It's somewhat debatable, but I guess, depending on which paper you read, anywhere from, I don't know, 13 to 18, somewhere around there, I kind of settled on 15, because I feel like that's what this original Amato paper showed. So I think of 15 as sort of my safe upper limit. Dead space fraction. So increased dead space fraction may be associated with mortality in early ARDS. Not all studies have been consistent in that finding, but not all studies have measured dead space fraction in the same way. So a little caveat there. So your end tidal CO2 over PCO2, though, also correlates with your dead space and degree of lung aeration, which has been demonstrated radiographically, which is nice because it's like this is a readily available marker at bedside. There are many caveats to this as well, which my colleague will be getting into in the next presentation. But this may be useful to think about when you're titrating PEEP. So if your end tidal CO2 to PCO2 ratio is decreasing as you're increasing PEEP, think about alveolar over-distension. Again, this means your dead space is increasing while you're increasing PEEP. With your goal of increasing PEEP, of increasing lung aeration, if you hit a tipping point where your dead space starts to increase, that may well be what's happening. As with just about everything I'm gonna talk about, there are caveats to this as well. So responses to PEEP don't always happen right away. They may be delayed. They may happen over hours. Caveat number two is data on applying dead space fraction to ventilator management is, as of now, very minimal. So speaking of bedside application, what do we do with this at the bedside? So again, you wanna start with lung protective ventilation. This is really the only strategy that we know improves outcomes in ARDS. But think about things like tidal volume and dead space when you're fine-tuning your measurements. Don't veer away from lung protective ventilation, but use this as just another something to add on. Again, caveats, the benefit of incorporating these variables into ventilator management's not yet known. It's pretty exploratory, and it needs to be fully evaluated. And then in critical care, we've seen a lot of situations in which improving physiologic endpoints does not always lead to improvement in patient-centered endpoints, and sometimes actually does the opposite. So again, when you are using these concepts, make sure you don't stray too far from lung protective ventilation when you're making ventilator adjustments. So this is an example of how these concepts may apply to my thought process when approaching a patient. So say you have, in this case, a 45-year-old woman with obesity, a BMI of 47, who's intubated for influenza ARDS. Comes to you from the emergency department, current bed settings, or tidal volume of 300, which corresponds to six mLs per kilo of predicted body weight. PEEP of 10, respiratory rate of 32. 100% FiO2. Plateau pressure here is 29. And your ABG is 720, 60, 55, with an end tidal CO2 of 34. So pretty big differential between your end tidal and your PCO2, suggesting a significant amount of bed dead space. So what do you do next? Proner. Proner? I think that's a good, that may be an, that's definitely something to think about. What else? PEEP titration, right? So PEEP titration. Sounds so simple, right? But these are like the options you have when you combine the high and low PEEP charts with ARDSNet. So there's room for a lot of adjustment within those ranges, right? So as you're titrating PEEP, look at what is happening to the patient. Of course, assess their hemodynamics. I don't have those in this chart, but if somebody is becoming hemodynamically more unstable, stop up titrating your PEEP. But in this case, we started out with a PEEP of 10, increased by two, and looked at the plateau pressure, driving pressure, compliance, and your end tidal to PCO2 ratio. So with this, so you can see that the driving pressure actually steadily decreases as the plateau pressure, as the PEEP is increased. So great, right? And the compliance, since that is a, since compliance and driving pressure are related, also improves as you're increasing your PEEP. However, once you get past a PEEP of 20, you can see that her end tidal to PCO2 ratio drops after that. So, you know, so we ended up leaving this patient with a PEEP of 20, and with that resultant plateau pressure of 31, so maybe like a smidge over your 30 cutoff, but with her BMI of 47, I was willing to accept that. And again, I don't, I wouldn't say that if her plateau were 41. You do not want to veer too far from lung protective ventilation. Her driving pressure is below 15. And again, her end tidal CO2 to PCO2 seems to kind of be at its best ratio here. So past that, since it's dropping, that suggests to me that we are over distending good lung, but not quite opening up at a lactatic lung. So compliance, like with everything else, you're measuring the compliance of the whole system. So an increase in compliance may not reflect what over distension's going on. So to summarize, considering driving pressure and dead space might be useful for optimizing ventilator settings, and incorporating these factors into clinical decision making should be an addition to lung protective ventilation and not a replacement. The benefit of adjusting ventilator settings to optimize physiologic parameters is not yet known. It needs to be further evaluated. And my colleagues will be discussing some of these issues with you in the coming lectures. Thank you. All right, so that gives a great segue to my talk. It's gonna be on volume cryptography, the dead space fractionator. I choose this picture. This is my first sunrise in Hawaii. And it taught me that a solution to a midlife crisis is a beautiful sunrise and an all-expense trip paid to Hawaii. So this is me. I am a intensivist in the CVICU at MedStar Washington Hospital Center. And the objectives of my section are going to be more related to dead space. What it is physiologically, the basis of it, how it's important, how it can be calculated with the assistance of volume cryptography, and what's the utility of it at bedside in the ICU. So let's start with some basic physiology about ventilation-perfusion relationship because that is what the dead space is essentially used for. The function of the lung is simple. It takes PO2 from the alveoli into the blood. And it transfers PCO2 from the blood to the alveoli and out through the exhaled tidal volume. So as you can see, oxygen is brought to the alveolar capillary membrane or the blood-gas interface by ventilation. And CO2 is brought over there by perfusion. So both of them have a sort of opposite or a mirror relationship. So this relationship is more indicative or is more reflected inside the alveolar gas because the alveolar gas concentration of oxygen and CO2 is contingent upon ventilation and perfusion respectively. And this difference may not be so apparent in blood gases, but when you look at alveolar gases through volume cryptography, you may be able to appreciate this difference a little more as opposed to arterial blood gases. So there are three ventilator-VQ relationships. And these are not distinctive entities. This is a spectrum. You can have a VQ of one, 1.5, two, or 0.8 all the way to infinity. So in a single lung dysfunction, there is a diverse amount of VQ mismatches, which needs to be appreciated through a different methodology. So VQ of one is normal. You have oxygen coming in. It diffuses easily to the mixed venous blood, oxygenating it, and PCO2, excuse me, or carbon dioxide sort of goes into the alveoli and gets ventilated out. The other relationship is a VQ of zero, which is number three, in which there is no ventilation but adequate perfusion. So the alveolar gas is gonna be similar to your mixed venous blood gas. So it's gonna be CO2-rich, oxygen-deficient. And the last one is a VQ of infinity, in which you have normal ventilation, but you have no perfusion. So you're gonna have alveolar gas or expired alveolar gas, which is gonna be CO2-poor. So this is where volume capnography helps us by showing us what the carbon dioxide concentration of exhaled gas is. Next is dead space. Dead space is the fraction of tidal volume which does not participate in gas exchange. There are three kinds of dead spaces. There is the instrumental dead space, which is your airway apparatus, the endotracheal tube, the tubing, and so forth. The length of the endotracheal tube, the longer it is, the more dead space you have, hence tracheostomy, less dead space. The bigger or the higher diameter of the endotracheal tube, the more dead space you have. So an eight or a seven is more dead space as compared to a six or a five. The next dead space is physiological. It can be divided into three compartments. One is alveolar, which is on top over here in the blue. It is well-ventilated alveoli, but bad perfusion. This is the upper lung zones. In a normal person, obviously in ARDS, it could be anywhere where you have damage to the alveolar capillary membrane. Anatomic dead space, this is the cartilage before the alveoli, the trachea, the larynx, the pharynx, and everything else that does not have blood supply. And then you have shunt, which basically means that you have well-ventilated, in which you have good perfusion, but you do not have ventilation. So this could be an intrapulmonary shunt or an intracardiac shunt as well. So the first person to take on this task of calculating dead space was Dr. Bohr in the 19th century. He determined that the tidal volume can be divided in two components. One is dead space, which is CO2-poor, as you can see over here, does not participate in ventilation. And the other one is the alveolar gas, which participates in ventilation, hence has a high PCO2 or a high CO2 concentration in it. If I would like to turn your attention towards this equation over here. So what it basically tells you is that the volume of CO2 concentration expired gas is equal to the volume of CO2 concentration, the alveolar gas, because that is the only gas that is participating in ventilation. So the volume of CO2 in a gas is the volume of the gas multiplied by the fraction of CO2 concentration. So tidal volume into expired CO2 is the volume of CO2 concentration expired. Tidal volume, which is equal to the alveolar volume, which is tidal volume minus dead space into the concentration of CO2 in that gas. After a lot of math, which I will not go into, he came up with this, which is the dead space fraction, which is dead space divided by tidal volume. And it is essentially the difference between the concentration of alveolar CO2 minus the concentration of CO2 in the exhaled gas divided by the concentration of CO2 in the alveolar gas. Since fractions, when multiplied by the pressure of the gas is equal to partial pressure of the gas, this formula can be rearranged into this, which is the difference in partial pressure between alveolar and exhaled gas divided by the partial pressure in the alveolar CO2. So this was the formula that was initially used to calculate dead space. However, there were some limitations to this formula. One was that there's no homogeneity in the measurement of alveolar CO2. Back then, they were using direct calorimetry to determine alveolar CO2, which required breathing into a bag, and then it was a little more complicated than just volume cryptography. And it was unable to differentiate between anatomic and alveolar dead space because we're assuming that all dead space has no CO2. But as we see moving on, that there is an entity called alveolar dead space in which there is some CO2 coming out. This was modified by Dr. Enghoff in the 20th century, who replaced the alveolar PaCO2 with the arterial partial pressure of CO2. And the benefit of this was that the arterial PaCO2 was somewhat a mixed product of all the lung units as it goes through all the alveoli, and was more indicative of alveolar CO2 as opposed to the PaCO2, which may be subjected to heterogeneity and may not be truly reflective of the average of the alveolar CO2 concentration. There are certain limitations. Your PaCO2 might be higher if you have a shunt in which you're sort of bypassing all the alveoli. And if you have an intrapulmonary intracardiac shunt, this might be higher, and you might think that there's dead space coming from alveolar dead space as opposed to a shunt. Moving on, Dr. Stupfel and Dr. Sevrigos were, they were more sort of in line with the future generations, and they didn't want us to go through all of this. So they simplified the entire equation. They said instead of using the concentration of CO2 in the expired gas, we can just use the end tidal CO2, which is readily available with a volume capnography. So the previous formula in which we were using PECO2 as a difference between the PCO2 and the alveolar gas, he just replaced it with PE, with the end tidal CO2. And there is a good correlation between the arterial and end tidal CO2 with the alveolar dead space, and this is what is most commonly used at bedside to calculate the dead space fraction and the amount of dead space that we have. As you can see, it correlates with alveolar dead space, and the higher the difference is, the more dead space you have. The normal value is four, so as you go higher, the more, you have more and more dead space. This schematic is sort of a good vantage point to use when you're at bedside. So if you have someone that you're concerned has increased dead space, increased physiological dead space, the first thing you wanna do is sort of use your initial formula, which is the arterial CO2 minus the end tidal CO2 gradient, or the alveolar dead space fraction, which is essentially the gradient divided by PCO2. If this is high, then you are sort of trying to determine what's the mechanism of dead space. Is it a physiological dead space, which means good ventilation but no perfusion, or is this a shunt in which blood is just either going to non-ventilated areas or it's just bypassing the lung overall? Um, so if you go, if this is high, you sort of go down this path, and you calculate using volume capnography, you can calculate the Bohr's, you can use the Bohr's equation to calculate the dead space fraction, which is, as I mentioned earlier, alveolar minus axial CO2 divided by alveolar CO2. If that is high, you have physiological dead space, you have poor perfusion to well-ventilated alveoli. Then you can use the Engolf's equation, which substitutes the alveolar dead space with arterial CO2, and if that is high, and there is a disproportionate, I would say, dissociation between the Bohr's equation and the Engolf's equation, that is reflective of a shunt, as PCO2 is disproportionately high in shunting, as opposed to physiological dead space. You can also calculate the blood flow through the shunt divided by the total cardiac output using this formula, which essentially uses the O2 concentration from the wedge position minus PO2 divided by total arterial content minus total mixed venous O2 content as well. Next is, how do we calculate all these wonderful values? What we use at Bed-Stuyte is capnography. Capnography can be used in two ways. You can either use it volume, or you can use it by time. You have your partial pressure of CO2 on the y-axis or the fractional concentration of CO2 on the y-axis, and you have time or volume on the x-axis. How does capnography work? What it does is basically you're in line with gas flow, and when CO2 is emitted through exhaled gas, it gets absorbed. It basically, sorry, it absorbs a certain wavelength that is being emitted through an infrared light, and the light that gets reflected back and is picked up by a transmitter or detector is obviously missing that wavelength, and the amount of light that gets absorbed by CO2 is obviously directly proportional to the fraction concentration or the partial pressure of CO2. You can do this mainstream, which means you're in line with gas flow in the same plane, or you can do it sidestream, in which you have your capnography sort of in parallel to gas flow, and it sort of has a sample chamber which analyzes the gas and releases it back to the expiratory lamp. Volume capnography, we're all pretty familiar with this. The first phase is tidal volume that is exhaled but does not participate in ventilation, so its CO2 is zero. Phase two is the interface between alveolar and anatomic, so you're sort of going from anatomic dead space into alveolar dead space, and you can see your CO2 going up. Phase three is where it flattens out, and this is just alveolar gas that is getting exhaled out, and it is a constant CO2 exhalation in the gas. Through this, you can sort of extrapolate and get all the values you need for your previous formulas. You can calculate the alveolar CO2, which is the midpoint of the alveolar plateau. This is the mean expired FeCO2, which was being used in previous formulas, and you can also calculate volumes from this, so this is the alveolar volume, since this is after the anatomic dead space and is all alveolar gas. This is the alveolar dead space. This is before you have alveolar that are truly ventilated, and this is the airway dead space, which is poor CO2 gas. Application, so how does this all correlate clinically? I will share my references in the end, so a lot of these studies have been done in the past, and there's a great reference paper by Dr. Magder from Toronto. She goes over all these studies one by one, so in ARDS, the dead space fraction was indicative of mortality, so higher dead space, higher mortality, especially when calculated through the NGOFS equation, which is more reflective of shunt, so shunt in ARDS is much worse because there's nothing to recruit. You can recruit your alveoli, but there's no blood flow over there. For PEEP, as Dr. Carter mentioned in her previous talk, you can optimize your PEEP as well, so if you have high dead space, and this is dead space is because of shunting, because of poorly ventilated alveoli that are being perfused, you can increase your PEEP, and with increased PEEP titration, if your dead space is going down, that's associated with increased oxygenation and successful recruitment, not necessarily mortality benefit, but you at least have better PO2s, and then to simplify everything, the end tidal CO2 and the alveolar PCO2 gradient is also associated with decreasing dead space fraction and associated with a successful prone position as well. Applications in PE, so increased dead space is associated with PE, good for diagnosis in the ER, is also associated with increased efficacy of thrombolysis as well, and for surgery, you can also use dead space fraction for better recruitment, and it's associated with successful weaning from the ventilator as well. This was previously mentioned. I'm running a little short on time, so I'm just gonna go through the rest of the slides. You can also use dead space fraction for one lung ventilation during thoracic surgery for optimal PEEP recruitment and for better weaning from the ventilator post-operatively as well, so lower dead space, better recruitment, better weaning from the ventilator. Cardiac output is something that can also be calculated through VCAP. Low cardiac output states are essentially a VQMS match because you have good ventilation, but you don't have good perfusion, so the same principle applies as it did previously. When you have low cardiac output, you have increased dead space. With increasing dead space, you're gonna have increased N-tidal to PCO2 gradient, so if you have low cardiac output and you have relatively normal lungs or lungs that are not actively deteriorating, your N-tidal PCO2 to arterial CO2 gradient can be reflective of a poor cardiac output. This is a busy slide, but just to go through it very quickly, N-tidal CO2 to PCO2 gradient or any equation for dead space fraction can also be reflective of pulmonary blood flow or RV output, so as you have more dead space generating through the course of a RV failure, it means that the RV output is decreasing, and as your dead space sort of decreases through any of the equations previously described, your RV output is improving. This is also very beneficial in right ventricular assist device weaning. As you're coming down, if your N-tidal CO2 to PCO2 fraction gradient is increasing, it's not the best time to come off the RVAT, but if it's improving as you come down on the RVAT speeds, that's something you can also use for weaning in assistance with other indices for right ventricular improvement. So just to sum it up, the purpose of this was not to flood you with a lot of equation, but is to sort of bring attention towards volume cryptography and its diverse use in the ICU, and what I hope I would do and everybody else is that when you go back, we sort of start looking at these indices in our practice and sort of see how they correlate with increased dead space, with decreased cardiac output, with successful weaning, with PEEP and everything else that I've mentioned before. Thank you for your time. These are my references, and please don't forget to evaluate this session in the app. Thank you. Next, we have Dr. Thind, who's going to be talking about ESOF vagal balloons and respiratory failure. Thank you, Yasir. Good morning, everyone. Very happy to be here. My name is Aman Thind, one of the intensivists at UCSF Fresno. My objective for today's talk is to do a bit of an overview of some of the physiological underpinnings surrounding esophageal pressure measurement. I really do want to focus on the physiology more so than the balloon itself. So we'll get right into it. We'll start by modeling the respiratory system with our single compartment model, which includes a single airway representing the resistive component, a single alveolus surrounded by the chest wall representing the elastic component. The equation of motion is basically a physical description of ventilation, and on the left-hand side we have the fuel that drives the ventilation with its two components, muscle pressure and ventilator pressure. So in a patient who is passive on the vent, the P must would be zero, and all the fuel would come from P vent. And this is actually the patient we'll be focusing on in our illustrations today for the sake of simplicity. On the right-hand side, we have two components of the ventilatory load. So we have the resistive load, resistance times flow, and elastic load, elastance times volume. And we'll come back to this equation a couple times. So we often have this intuitive idea that when we see high pressures on the vent, we get concerned about lung injury. And to that I want to say that we have to pay attention to what pressure we're looking at. We have to understand the physiological meaning of that pressure, and we have to realize that to assess lung stress, we have to isolate the pressure across the lung, which we'll try to find today. So we'll start with the peak pressure. This is the maximum airway pressure in a single breath, and this is a patient who has pretty high peak pressure of 52. That corresponds to this point right here on the airway pressure waveform. So peak pressure is airway pressure. So in our model, it's measured right here at the airway opening. In real life, this corresponds to the end of the ET tube. Now airway pressure is actually synonymous with P vent. So remember this equation. P vent is synonymous with airway pressure. So what that means is when you have a patient with high peak pressure, all that really means is that the vent is having to do a lot of work on the patient. That's all it means. This may be because of high resistive load, high elastic load, or both. So this patient was a patient with asthma. So in this patient, the peak pressure was high because of high resistive load. So in this patient, the resistance was high, and since this patient was passive, the P vent had to be high to satisfy the increased load. This is why the peak pressure was high. Now resistive pressure has absolutely no relevance for lung injury. So this energy is literally being spent on the airways. And this is the reason why peak pressure on its own should not be used to assess lung stress. So what about plateau? So this is the end-inspiratory airway pressure measured as zero flow conditions. So remember, you have to do that pause to measure this. So because the flow is zero, the resistive load at the time of measurement is zero. And this is because the resistive load is the product of resistance and flow. So the plateau pressure does filter out the resistive pressure. So back to this example, the plateau was only 24. So this is how we knew that in this patient, that really high peak pressure is because of high resistive pressure. So yes, the plateau does get us one step closer towards finding the truth as far as lung stress is concerned. But it also has its own limitations. So to really understand lung stress, we have to first understand this idea of transmural pressure. So this is an illustration of an elastic chamber, like a balloon or an alveolus. So the pressure on the inside of this chamber, we label intramural pressure. The pressure on the outside, extramural pressure. And the pressure across, transmural pressure, which is the difference of the two. Now, it's the transmural pressure that actually decides the degree of inflation and wall stress of this chamber. It's the transmural pressure that actually is the true distending pressure of an elastic chamber. So here's an example of three patients, of three balloons or alveoli. All of these have the same pressure on the inside. The first one, the pressure on the outside is zero. So the pressure across is 10. The second one, the pressure on the outside is five. So the pressure across is five. And that's why this balloon is smaller. The third one, the pressure outside is negative five. So the pressure across is 15. This is why this balloon is more inflated than the first one, has a higher wall stress. And this is actually how negative pressure ventilation works. This is how we all breathe. So we really have to pay attention to the pressure on the outside. So back to our model, plateau and PEEP are actually alveolar pressures. They're reflecting pressure at the alveolar level, which is the intramural pressure of the lung. So if you want to know the transmural pressure of the lung, you have to account for the pressure on the outside of the lung, which is the pleural pressure. This is the key point here. This is where the balloon comes in. So the esophageal pressure happens to be a good surrogate of pleural pressure. Now how to do it at bedside is a discussion for another day. But when you do use the balloon, you are able to calculate this thing called transpulmonary pressure. And you can do that during inspiration, where we get an inspiratory transpulmonary pressure. And this is plateau minus inspiratory pleural pressure. Or during expiration, where you get an expiratory transpulmonary pressure, which is PEEP minus expiratory pleural pressure. Now you can think of these two transpulmonary pressures as the plateau and the PEEP that the lung actually sees. And so these really are better measures of lung stress. OK, so what about driving pressure? So driving pressure is the new kid in town, right? So we often use this every day to try to ensure safe ventilation. So this is how this works. So during expiration, the pressure at the alveolar level is PEEP. In comes the tidal volume. The pressure is now plateau. So driving pressure is basically the difference between plateau and PEEP. However, notice that this pressure is being spent to expand not just the lung, but both the lung and the chest walls, as our model suggests. So this is why driving pressure is influenced by the compliance of both the lung and the chest wall. So if you want to isolate the pressure spent on expanding just the lung, you would have to look at transpulmonary driving pressure, which is the difference between an inspiratory and an expiratory transpulmonary pressure. And if you do the math, that equates to being equal to the difference between driving pressure and the change in pleural pressure with passive inflation. Here's a schematic description of the same. So the total length of these bars is representing the total driving pressure, or the driving pressure of the respiratory system. Then the smaller bar on the top, then, represents the fraction of driving pressure that's being spent on the chest wall, and the one on the bottom, the fraction being spent on the lung, which we call the transpulmonary driving pressure. All right, so what's the clinical relevance of all this? So the biggest problem with our usual thresholds of plateau and PEEP that we use every day is that we don't account for the individual differences in chest wall mechanics in our patients. So a PEEP of 10 and a plateau of 30 do not equate to the same degree of lung stress in everybody. Now for the average patient, it's probably OK. But in patients with extremes of chest wall mechanics, that is not OK. And these are the patients who benefit the most from esophageal pressure measurement. So there are two broad categories of abnormal chest wall mechanics. There are conditions with heavy chest wall and conditions with stiff chest wall. Heavy chest wall, the big example here is obesity. And the big problem here is that all that extra weight on the chest increases the pleural pressure during expiration. So the main issue here is that there's high pleural pressure in these obese patients. So here's an example of that. So say you have two patients, BMI of 20, BMI of 60. They both have severe ARDS. And the PEEP table tells you to set a PEEP of 24 in both of these patients. The first patient is lean. So the expiratory pleural pressure is 4, which is normal. So if you were to set a PEEP of 24 in this patient, the expiratory transpulmonary pressure would be 20. Now, this is really high. This number should be close to 0. So this patient is getting too much PEEP. On the other hand, the obese patient has an expiratory pleural pressure of 24. So the transpulmonary pressure of this patient is 0, which is optimal. So the PEEP for this patient is optimal. So the big message here is that in obese patients, the optimal PEEP is much higher than lean patients in order to overcome that extra pleural pressure. Quite interestingly, the chest wall compliance is actually normal in obesity. And this was studied in 2010 by an elegant study by Stephen Loring and his group. So the chest wall in obesity is heavy but not stiff. So the driving pressure can actually still be useful here. So this is a real-life example of an obese patient with a plateau of 34 and a PEEP of 24. So you may be worried about that PEEP of 34. But if you look at the driving pressure here, it's only 10. So that reassures us that our ventilation is safe, which is, in this case, confirmed by the inspiratory transpulmonary pressure of 14, which is safe. So I actually use this strategy in patients who are obese but don't have a desophageal balloon. When I'm ramping up my PEEP, I pay close attention to the driving pressure, and if that number is safe, then that reassures me that my ventilation strategy is safe and I'm not over-PEEPing the patient. The most extreme example I remember, which I don't have a picture of, unfortunately, was a patient, we had to set a PEEP of 30, and the plateau was 40, but I was okay with that plateau because the driving pressure was 10, and that was later confirmed by the balloon. All right, so what about stiff chest wall? So this is the second category. The most common example is intra-abdominal hypertension. We don't often realize that diaphragm is actually part of the chest wall, so all that extra pressure in the abdomen stretches the fibers of the diaphragm, therefore causing a stiff chest wall. The formula for chest wall compliance is tidal volumes divided by the change in pleural pressure. So when you have a stiff chest wall, with the same tidal volume, you're going to have a much higher increase in pleural pressure with passive inflation. Here's an example of that. So here's a patient with intra-abdominal hypertension, where during expiration, your pleural pressure is 14. It's a little high, and this is something that's unique to intra-abdominal hypertension because a part of that extra pressure gets transmitted up to the thorax. But anyways, the kicker here is that after inspiration, the pleural pressure jumps from 14 to 28. This is really abnormal. This is the key characteristic of someone with a stiff chest wall. So the plateau here is 38, which may be concerning, but if you look at the end-inspiratory-transpulmonary pressure, that is 10, which is within safe limits. So this is the kind of the patient where the balloon can be really, really helpful. Why? Because you can't even use driving pressure here. And here's the reason for that. So back to our little schematic here, and we'll add some numbers this time. So this is an example of a patient with normal chest wall with a driving pressure of 15. So normally, more than half, in this case, 9 out of 15 is spent on the lung, which is what we refer to as transpulmonary driving pressure. In obesity, this proportion does not change. So this is why we are able to use driving pressure in obese patients. However, this proportion does change significantly in patients with stiff chest wall. So in this example, you have driving pressure of 27, but most of that is actually being spent to expand the chest wall. And only 9 out of 27 is being used to expand the lung, which is actually the same as the first two examples. So this is an example. This is a reason why you cannot use driving pressure in conditions with stiff chest wall, the usual thresholds. All right. So in conclusion, peak pressure incorporates resistive pressure. So this is why, on its own, peak pressure is basically useless, in my mind, in trying to assess lung stress. Plateau and PEEP, they do filter out the resistive pressure, but they represent only the internal intramural pressure of the lung. By subtracting the pleural pressure, the transpulmonary pressures, they do reflect the pressure across the lung, and are therefore better measures of lung stress. And these pressures are most useful in patients with abnormal extreme chest wall mechanics. Driving pressure is the pressure spent on expanding both the lung and the chest wall. And the usual driving pressure thresholds can be still useful in a patient with heavy chest wall, but not in patients with stiff chest wall. And with that, I thank you for your attention. All right. Next up is Dr. Fan. He's going to talk about EIT. Okay. Thank you for the kind invitation to speak. I think this will work well with the physiologic setup from the previous speakers. So I'm going to speak maybe less about physiology, more about clinical application, or maybe what little clinical application we know about for EIT at the moment. I understand that now this device has most recently become approved here in the United States. It's actually been Health Canada approved, where I practiced for over 10 years. Here are my disclosures. I won't be speaking about any specific devices. Maybe germane to mention that I did previously, over 10 years ago, receive honoraria and research support from Draeger. That makes the EIT device for research on EIT, but that's been elapsed. Okay. So the whole idea here for EIT, or any of the things that we talked about, is that we understand that ARDS is a heterogeneous disease. It's heterogeneous in space, and it's heterogeneous in time. Starts off inflammatory, then becomes bi-proliferative. And even when the chest x-ray looks relatively homogeneous, the chest x-ray is a blunt instrument to look at things. And really, this nice article summarizing really decades of research from Luciano Gattononi and his colleagues in Milano, showing us that when you use CT scanning, you really start to appreciate the spatial heterogeneity of the disease, right? We got lots of collapse, flooding, and inflammation, and problems in the dependent lung zones and maybe less or more spared aerated regions in the non-dependent lung zones, giving rise to this idea of the baby lung concept of ARDS. In an adult-sized patient, we only have functionally a baby-sized lung available for ventilation. And as Dr. Kadir was saying, when we ventilate, unfortunately, the ventilator is also a blunt instrument. You tell the ventilator to deliver tidal volume or pressure, it delivers it to the whole lung. It really doesn't care how much is collapsed, how much is open, how much is sideways, up or down, or whatever. It just does what you tell it to do, right? And so how you distribute those mechanical forces to this injured lung obviously leads to problems. And this is amplified by the fact that it's inhomogeneously damaged. And this is something we've known for a very long time. So here's the physiology part. This is a really nice mathematical model by Jeremy from Boston, published in the 70s, showing that we know that the alveolar structure of the lung, if it's inhomogeneously damaged, collapsed, consolidated, or that sort of thing, that areas that are consolidated, the surrounding alveoli, they don't expand normally, and you get this amplification of stress that we've been talking about that's delivered by the ventilator, so that what seemingly should be normal on the ventilator screen can actually, you have regional differences in stress that could cause further lung injury, damage, and rupture. Of course, there's no good mathematical models without a corresponding, they actually made a physical model out of condoms, actually in the 70s, to model how they would, what would happen when they expand the lung, and this sort of idea. Of course, again, the idea that when you have homogeneous expansion, everything sort of looks good if you think about the alveolar structure of the lung as a honeycomb sort of kind of thing, but when you have a collapsed region, which is the dark gray bar, the surrounding alveoli, they don't expand normally, and again, at those interfaces, you can get stress raisers or amplification of stress that's very important for Vili. And we know that globally speaking, the more inhomogeneous the lung is, and again, I would say this is a good surrogate for severity, right? The more severe the lung injury, the more severe the RDS, the worse it is for patients. And again, this is a nice study from Massimo Cressoni and Luciano Gannoni showing that as you increase the amount of inhomogeneity as measured by quantitative CT scanning, you have an increasing odds of mortality or bad outcomes, okay? And again, this is probably just a really, another surrogate for severity of lung injury. So the more inhomogeneous the worse, so if we could do things to make ventilation more homogeneous, perhaps we can reduce the amount of lung injury and improve outcomes. So this is a regional problem. So it's characterized by this heterogeneity that we talked about, or this inhomogeneity, so then we need some kind of regional monitoring, okay? So the idea, that's what EIT is about. So maybe we should, or the balloon, or these sort of CT scanning, I don't know about your ICU, my ICU, it's not easy to send patients to the CT every time you want to make a ventilator change, probably not a very useful sort of tool at the bedside, as it might be in some units in Italy. But the idea is that we can use some of these bedside tools, whether it's lung ultrasound, sort of more monitoring of respiratory mechanics at the bedside, and maybe this tool, electrical impedance tomography, to understand the regional differences in inhomogeneity, and then again maybe modify our ventilator settings, we've already heard a lot from the speakers, things like proning, PEEP, you guys all gave good examples, that can increase the homogeneity, increase the homogeneity of ventilation distribution, and again that might lead to less lung injury and better outcomes. So this tool, electrical impedance tomography, is that idea. So rather than going for a CT scan, you attach this belt, it's a non-invasive, radiation-free method, where you put a band of electrodes, this is a slide from my colleague and friend Tom Perrino, who's a respiratory therapist, everything I know about mechanical ventilation is from Tom when I was a resident and fellow working in the ICU, but he's done a lot of work and research on electrical impedance tomography, and it's a belt you put on the chest of the fourth to fifth intercostal space, it basically sends electrical signals you can see through the chest as the patient is breathing or the patient is being ventilated or some combination of the two, and you get this sort of image that's the impedance of that electrical signal going through the belt to the various electrodes, and the impedance is a surrogate for how much ventilation or how little ventilation there is in this image, and because it's happening 50 cycles per second, the image is dynamic, so you're actually visualizing the breathing, and so maybe the only plug here is I think actually the byline or the advertisement for Draeger's machine is something like visualizing ventilation or something like that, but that's the idea, so at this slice of the lung, what you're seeing is the breathing go in and out by the changes in impedance from the electrodes around the chest. So that's the picture that you can see here, so when the patient is breathing, you can see that the changes are coming in and out, and that represents changes in impedance, which represents changes in ventilation. The brighter the image, the more the ventilation that's there, the bigger the change in impedance, the darker the color, the less the change in impedance, the less the ventilation that's happening in those images, and you can get global or regional distribution, so sometimes you can look at regions of interest, so you could either think, again, if you're thinking about the inhomogeneity from supine to prone position, you might want to look at regions of interest from ventral to dorsal. Sometimes when you're thinking about inhomogeneity, that's maybe more unilateral lung injury or pneumonia or infection or something like that on the x-ray, you might think about quadrants, but there's different ways that you could look at the images, and then again, the idea we already talked about, the brighter the area, the bigger the change or the more the ventilation, the darker the imaging, the less ventilation and the less evenly distributed ventilation, so the idea here is that you can look at the image and have actually a qualitative appreciation for how homogeneous or inhomogeneous the lung is, so for instance, if you have pretty much right lung atelectasis, you might see an image where there's only brightness on the left side and really nothing, no ventilation, no changes in impedance on the other side. That would be an extreme example, but you could actually visualize in real time what changes or inhomogeneity there is. Apart from that, you can get a lot of quantitative information from this device. I don't even want you to read what's on this slide. The point of this is that, one, this is a very nice review article that's quite current. You can find it online if you want to read about electrical impedance monitoring, but there's a lot of derived measurements, if you could. Some of them in real time you can get from the machine. Some of them you have to do offline processing to understand, and these are all, again, surrogates for recruitment, lung volume, changes in tidal variation, how homogeneous the lung is being ventilated and all sorts of things, and again, I would say these are interesting things that you could get from EIT. None of them, I would say, have been tested in rigorous clinical trials to tell us that they're useful for setting anything on the ventilator, so really an intense interest in researching these parameters at the bedside, but really not useful for routine clinical practice at the moment. You can use EIT, and it's being researched for all kinds of questions, right from the pre-invasive mechanical ventilation, like patients on non-invasive ventilation or high flow nasal oxygen, all the way to when they're off or getting ready to come off for liberation, spontaneous breathing and that sort of thing, to monitor all the various forms of ventilation that are occurring and to ensure, again, as much as possible, that the settings that you're providing are trying to lead to a more homogeneous distribution of ventilation. I'm going to focus, as many of my colleagues today, on the idea of setting PEEP with EIT because this is a good example of how EIT is most commonly being used in units that have this device and probably the area that has the most intense research that's available for EIT. Okay, and we're interested in using new, fancy devices for EIT because we'll be talking at CHEST 2045 about what the optimal PEEP for ARDS is, right? Like, nobody really knows. I mean, sometimes in the ICU, I like to shake my magic 8-ball and the answer is always 10. But even like in Brussels many years ago, Luciano said, after 40 years, we still don't know how to set PEEP. I would say that's still the challenge, but of course, in these cases, we want to use some tools because, especially in the difficult cases, I would say, I'm going to sort of keep it simple. I use the PEEP FIO2 table for almost every patient, and when that patient doesn't respond in a way that I feel is reasonable or as I predicted for PEEP, and again, it's at the margins, the very obese patients, the very stiff chest wall patients, they have chest surgery or abdominal surgery or chest trauma, these are the ones that you might want to use these additional tools to customize the PEEP setting. And so the idea here is that you can use electrical impedance tomography to look in real time at changes in impedance. So at the top, what you can see is that you see changes in end-expiratory lung impedance, and this is something that's monitored on the bedside. So one, you can get the blue images, so you can watch the nice breathing going on, but you also get the waveform that sort of tells you what the impedance at end-expiration and inspiration is, and end-expiratory lung impedance changes is basically a circuit for end-expiratory lung volume. So as you change the PEEP, changes in end-expiratory lung impedance are like changes in end-expiratory lung volume. So the bigger the changes, the bigger the recruitment or the bigger the lung volume that's available, the smaller the changes, the smaller the lung volume. You can also get these interesting changes in the orange here, ODCL, which is the overlap between as you change the PEEP, you could see how much is over distended versus is being collapsed, okay? And the idea here at the bottom is that you try to find the intersection of where you're maximizing the...you're trying to maximize the amount of lung that's, again, being homogeneously ventilated. There's very little over distension, there's very little collapse, and where you see that crossing point is, is probably the optimal PEEP, at least by EIT standards. So you could see in this decremental PEEP trial here, that basically when you get to a PEEP of about 14, you see the crossing of those lines, you sort of have very little, maybe you sort of have some over distension, but it's down from when it was PEEP 18. You have a little bit of collapse happening here on the right dorsal area here, but that's the sort of like the optimal area where those two are intersecting. So this is, again, sort of the bedside application of these things where you might decide PEEP based on electrical impedance demography. We have actually a few randomized control trials testing this strategy in ARDS patients. This is the first, actually, this is not a randomized trial, but it's a retrospective study that sort of kicked things off showing that in this Chinese study that EIT guided PEEP versus using a pressure volume curve or using, again, respiratory mechanics to calculate PEEP setting actually led to improved oxygenation, less severity of illness, better driving pressure, better static lung compliance, but it didn't lead to any benefits in clinical outcomes. So it seemed to improve physiologic parameters, but that didn't translate into clinical benefits. Again, this was a relatively small study, 55 patients, so it may be hard to make, and retrospective, so it may be hard to make any firm inferences. But again, I just caution you because this is the recurring theme in critical care, right? And I think Dr. Kadir mentioned this, is that studies that showed improvements in physiologic measures in critical care often, unfortunately, didn't lead to benefits for patients. So the fact that we can improve oxygenation or we can improve ventilation or reduce dead space, sometimes those things didn't improve clinical outcomes, even though we thought it was good because it improved those physiologic surrogates. This is why we need to test these things in randomized trials. So recall that in the ARMA trial and in Proceva, the groups that got randomized to proning or low tidal volume had worse oxygenation on day one, but they all derived the mortality benefit of those interventions. So that's why it's important to test these sorts of strategies in clinical trials. Okay, so one of the first two clinical trials is, again, that same group in China went on to randomize 87 patients to this idea of using EIT-guided PEEP versus pressure volume loop-guided PEEP. And what you can see here is that, interestingly, again, both methods actually, apart from clinical setting by the team at the bedside, led to improved oxygenation, driving pressure, static compliance. There was actually significantly lower driving pressure in the EIT group. And this actually translated into lower mortality in the group that received EIT. Now, again, there was, because it's a very small study, there were some imbalances in baseline characteristics. There's likely some confounding that still existed, even though it was RCT. But again, a proof of the concept that it's interesting that the idea that EIT-guided PEEP both led to physiologic benefits, and at least here, translated to the idea of maybe some clinical benefits. But then you have a subsequent study, slightly larger, just over 100 patients. Again, EIT-guided PEEP here versus the PEEP-FII table led to changes in PEEP in many patients. But unfortunately, in this study, it didn't lead to any clinical benefits for patients. So again, conflicting results from these two randomized control trials. So we need more studies and bigger studies to better understand where the EIT could be used to set PEEP in these patients. You can use this thing. It can be used all over the place to set PEEP in all kinds of situations. So something near and dear to my heart is ECMO patients. So in France, they're using EIT to set PEEP in ECMO patients, where mechanical ventilation of these patients is still challenging. We don't know what the optimal settings are. But here, again, they're using the idea of finding that balance between overdistension and collapse, and finding where the nadir of those two things are. And that would be the optimal PEEP for those patients. And you can see three examples here, where the PEEP is very different based on the EIT averages and that intersection of overdistension and collapse. It's also been very useful in COVID-19. These are my colleagues at St. Michael's Hospital, led by Laurent Bruchard, who again showed in a very large group of COVID-19 patients that you can actually stratify patients using the recruitment to inflation ratio to understand low, medium, and high recruiters. And that EIT would result, again, in, as you might expect, different PEEP settings, depending on the degree of recruitability. So in the high recruiters, these patients responded to a much higher level of PEEP, a medium of about 16. And in the low recruitability patients, they didn't really have a really good response to PEEP. And the EIT suggested, again, in the balance of overdistension or collapse, the PEEP was optimally set around 10. So it could be very useful in those settings. Bob Heisey's group in Michigan has shown that actually reductions in PEEP, so most often actually EIT seems to lead clinicians to reducing PEEP to reduce the amount of overdistension and perhaps balance the amount of collapse that occurs. So typically, in these patients, almost two-thirds are typically getting a reduction in PEEP rather than an increase in PEEP. And interestingly, that also translates to a decrease in mechanical power. Here he's shown in this nice pilot study. And again, we're now thinking that a more holistic measure of lung injury could be this concept of mechanical power that not only includes driving pressure, PEEP, and tidal volume, but again, things that we don't commonly think about, respiratory rate, maybe flow, also very important targets for a lung protective strategy. The challenge, of course, is that then if you want to show this to some of the other methods that we heard about from the panel, it's like you're going to get different results. You want to compare EIT to the balloon or to something else, it's going to tell you that the optimal PEEP is different in different cases. So this is why we need sort of better comparisons, perhaps less to the PV curve, but maybe to standard tools like the PEEP-FL2 table to understand the role, the better role of EIT. Okay, I'm going to finish quickly because we're out of time. But basically, you can use this also in other reasons. We're not going to talk about like spontaneous breathing and maybe this idea of P-Silly because that could be also very challenging. Sort of newer EIT machines also can look at perfusion, so you could gate the images for perfusion so you could look at VQ matching or mismatching, which also might be very useful in these situations. And I just want to finish with the idea that, again, new tools are great, but we just want to be careful, okay, because when we want to apply monitors in and of themselves can't save lives, right? Putting a piece of plastic like a swan-gans catheter or applying a belt to a patient isn't going to save their lives. It depends on what information you get from that device and what you do about it that's going to change patient outcomes, right? Putting an art line isn't going to save a patient's life, but what you do to that. So we need not just to understand what we measure, but what the treatment algorithms that we couple to those measurements, and that's what we need to test in clinical trials. We have lots of clinically interesting monitoring devices that have shown no improvements in mortality, and so we just want to be careful about for the future. So to summarize, EIT is a non-invasive bedside tool for monitoring regional ventilation. It could be useful for many clinical questions. I gave the example of PEEP titration, where it could be very helpful. We need more studies. So at the present time, again, I would say in our ICU, we limit it to challenging cases where we try to titrate PEEP, but it doesn't go kind of how we expect. Remember the three rules, monitoring alone can't save lives. We need future trials to sort of understand an EIT-guided treatment strategy that might improve PEEP, homogeneity, something like that, that might lead to a more personalized sort of type of mechanical ventilation. So thanks very much.

EIT

Electrical Impedance Tomography

non-invasive bedside tool

regional ventilation monitoring

lung homogeneity assessment

changes in impedance visualization

ventilation distribution

optimal PEEP levels

ARDS patients

ventilation monitoring on ECMO