So, thank you all. Today I'm going to talk about respiratory mechanics and monitoring. I'm Robby Kamani from the Department of Anesthesiology and Critical Care Medicine at Children's Hospital Los Angeles. Here are my disclosures, although none are really relevant for this talk. So, respiratory diseases in general are crucial for us in pediatric critical care, and as we can see here, lower respiratory tract infections, as an example, still are the most common cause of death for children under the age of five. Now, the approach that I like to take as I think about the respiratory system is a compartment-based approach. There are many compartments of the respiratory system that can contribute to respiratory failure. There's the CNS compartment. There's the extra thoracic upper airway compartment. There's the within the thorax compartment, which is comprised of both the lower airways as well as the pulmonary parenchyma, and then there's a sort of extra thoracic compartment, which includes the muscles of the respiratory system and peripheral nervous system. So I'd like to take that approach as we talk about respiratory mechanics and monitoring using examples from each of these areas. So the first that we'll start with is the upper airway, and here are the board principles as we think about the upper airway. Understand the location of potential obstruction of the upper airway, supraglottic, glottic, and subglottic, as well as differentiating a fixed obstruction from a variable obstruction. Understand flow pressure dynamics for flow limitation, how the airway caliber may change with spontaneous versus positive pressure, rationale for therapies used to treat upper airway obstruction, and age-related airway dynamics. Let's start first with the anatomy, and there are really many characteristics of the pediatric airway that make it more subject to upper airway obstruction than the adult airway. Children have a relatively larger-sized tongue to the size of mouth with a more rostral larynx and an epiglottis that is differently shaped here, with a more omega-shaped epiglottis in the pediatric patients here as compared to the flatter epiglottis that you may see in the adults. In addition, the larynx has this more classic funnel shape that narrows further as you go down. Furthermore, the pediatric airway is simply smaller, and so the effect of edema, let's say from an endotracheal tube or from croup, is larger in the pediatric airway as compared to the adult airway. And this is given by Pousseau's law, where the resistance that goes through that tube is proportional to one over the radius to the fourth power under conditions of laminar flow. And under turbulent flow, this is one over the radius to the fifth power. So that same potential reduction, let's say, of one millimeter of edema in the pediatric airway will have a much larger change on the circumference of the pediatric airway and a subsequently much larger resistance in the pediatric airway as compared to what you may see in the adult airway. Now, a major determinant of whether flow is turbulent versus laminar is based upon the Reynolds number, which can be conceptually thought of as the ratio of inertia over viscosity. So flow is more likely to be turbulent as the Reynolds number increases, i.e. in circumstances where the velocity increases or the density is high. And this is the theoretical basis for why heliox or helium-oxygen mixtures may help in situations of upper airway obstruction by trying to reduce the Reynolds number by decreasing the density of gas by substituting helium rather than nitrogen in the mixture. So as we start to think about respiratory mechanics, there are a few important principles to remember, the first of which is Boyle's Law. Boyle's Law says that the pressure and volume are inversely related to one another within a structure. And air will flow from an area of relatively high pressure to a relatively low pressure as long as there is a structure which is able to change in volume with walls that don't collapse in a source of work to change that volume. As we think about the respiratory system, the source of work that's used to change that system is the patient, typically with diaphragmatic contraction. The structure is able to change in volume, i.e. the intrathoracic compartment is able to get larger in its size, and then air will flow from a relatively high pressure in the atmosphere to a lower pressure in the alveoli as we lower the pleural pressure to begin respiration. And so as we think about this in application to our normal respiratory pattern in spontaneous breathing, how does this begin? The diaphragm contracts downward, that results in a lowering of the pleural pressure. This lowering of the pleural pressure then translates into a slight lowering of the pressure in the alveoli. This pressure in the alveoli now falls below atmospheric pressure and air flow comes in. What happens on exhalation is just the opposite. The diaphragm relaxes, that relaxation of the diaphragm results in a slightly less negative pleural pressure that then translates into a slightly positive pressure in the alveolus relative to atmospheric pressure, and hence you have exhalation. And as we go deeper into respiratory physiology, and this is an important concept in cardiac physiology too, we must remember the transmural pressure. A transmural pressure is the pressure across the wall of a structure, and it's the pressure inside minus the pressure outside. So the transmural pressure, as we think about the upper airway and the extra thoracic upper airway, is crucially important for us to understand why there are dynamic changes with inspiration and exhalation in the extra thoracic upper airway. So as we think about as somebody is taking a breath in under the normal circumstance, the pressure on the inside is the airway pressure, so that pressure is slightly negative with respect to atmospheric pressure. The pressure on the outside is atmospheric pressure, i.e. the transmural pressure on inspiration is slightly negative in this circumstance, minus 2, minus 0 for an atmospheric pressure, for example. And on exhalation, the situation is, of course, reversed in the extra thoracic upper airway, slightly positive within the airway compared to atmospheric pressure, which results in a slightly positive transmural pressure. So now what happens when there's extra thoracic upper airway obstruction? As an example, here you see this point of obstruction below the area of the vocal cords. So the patient is trying to increase flow across this area of resistance. To increase that flow, they generate more respiratory effort, bigger reduction in pleural pressure, which translates to a larger reduction in alveolar pressure, and a very negative pressure here in the extra thoracic airway at this point, distal to this point of obstruction, i.e. the pressure in the airway at this point may be very negative, let's say minus 25 compared to atmospheric pressure, and that's when we see further collapse of that upper airway on inspiration or dynamic upper airway collapse and inspiratory flow limitation. And here's a picture highlighting that from a lateral radiograph of a child with croup, as you can see during exhalation, the caliber of this airway looks relatively normal. But during inspiration, there is much more significant narrowing of the airway because of large swings in pressure during inspiration to try to overcome that area of obstruction with resultant transmural pressure that promotes collapse. Now how do we diagnose this? Well, the classic finding of extra thoracic upper airway obstruction can really be seen on a flow volume loop. In this circumstance, as we think about a spontaneously breathing patient, remember inspiration is down below, exhalation is down above, the dotted line represents a relatively normal appearing flow volume loop. And what we see classically in extra thoracic upper airway obstruction from croup is predominantly obstruction on inspiration that results in this pattern of inspiratory flow limitation, i.e. flow is capped at a certain level and you have this flattening portion of the flow volume loop with relative preservation on exhalation. Now the tidal volume is a little bit less because oftentimes the patient can't get in as much tidal volume. In contrast, if we've got an area of more fixed obstruction, even if it is in the extra thoracic space, this can be either intra thoracic or extra thoracic, if it's fixed, you'll see that lesion on both inspiration and exhalation. And an example here would be, for example, complete tracheal rings where you see this flattening on both inspiration and exhalation. Now in truth, to really diagnose inspiratory flow limitation, you also need a measure of effort. You need to know that the patient is trying. And so here you can combine flow on this axis with pressure on this axis as measured by esophageal manometry. And this is a patient with croup, a child with croup, and what you see is this very classic pattern of inspiratory flow limitation where the patient is continuing to pull negative pressure on the esophageal pressure, but flow does not increase, flow stops and plateaus. A patient gets racemic epinephrine, now you see that pattern goes away, that the peak flow occurs with a relatively modest delta esophageal pressure without any flattening across the top. And this can also occur even if the area of obstruction is superglottic. And here's an example from a patient with superglottic obstruction from poor airway tone and obstructive sleep apnea where you see that same inspiratory flow limitation, flattening of the flow waveform with a reduction in airway pressure. This patient is now getting an airway maneuver, a jaw thrust, and what happens is you give the jaw thrust, that now goes away, flow gets much higher with a much lower pressure, remove that flattening portion, let go, and the airway obstruction again has come back with inspiratory flow limitation. And these effects are not just limited to the airway with further flow limitation and dynamic collapse of the airway, but of course there are important cardiopulmonary interactions that come into play here with severe upper airway obstruction, especially pulsus paradoxus. As these patients further decrease the interthoracic pressure, this results in increased afterload on the left ventricle by increasing the transmural pressure across the left ventricle and potentially compromising cardiac output. Okay, so the next compartment that we'll move on to is now going intrathoracic and start to look at the obstructive lower airways disease. Here are the board principles for lower airway disease, understand airway and tissue resistance to airflow, airway resistance and the effect of the pressure-volume relationship of the lung, understand lung volumes and health and disease, flow-volume relationships during both tidal breathing and forced exhalation, as well as gas flow limitation and the applicability to pulmonary function testing. So when I'm talking about lower airway obstruction, this is a perfect example. This is a bronchial with severe asthma, lots of inflammation around here with clear constriction of this bronchial. And in fact, bronchospasm can be quite dramatic. Here's just an image of a picture of a bronchi before and after vagal stimulation, and you can see how much the caliber of the bronchi may change. Now, why is it that pediatric patients seem to struggle the most with lower airway obstruction? Well, this has to do with changes in anatomy. As we look at the cross-sectional area of the airway from adults, what we see is the most limitation in cross-sectional area, of course, comes through the first several generations of airways. But then very quickly, once you get out closer towards the peripheral airways, there is a dramatic increase in the cross-sectional area of the adult airway. And as we look at the relationship between age and conductance of both central and peripheral airways, and remember, conductance is simply one over the resistance, right? That the central airways stay relatively constant across age, but there is this very large change with an increase in conductance or a decrease in airway resistance in the peripheral airways once you reach about four to five years of age. And we can see that nicely here in this animal model of the peripheral airways, that as we go from infant to child to older child to even the adult, now the cross-sectional area of those airways is much larger here on the adult side as compared to the infant side with the peripheral airways. And this is why infants and children, therefore, are much more prone to diseases which affect the lower airways and increase that resistance because they simply don't have the same cross-sectional area available. And again, the concepts of transmural pressure become important to better understand the respiratory mechanics during lower airway obstruction. So here we're concerned about the transmural pressure on exhalation. And under normal circumstances, remember, the transmural pressure is the pressure inside minus the pressure outside. So when a patient is exhaling, the pressure within the intrathoracic airways is slightly positive relative to the pressure outside it, which would be the pleural pressure. Because remember, the pleural pressure is slightly more negative under normal respiration than the pressure in the airway. But then what happens with progressive lower airway obstruction? Well, the problem is that the area of obstruction here is in the intrathoracic space, right? So as that obstruction becomes larger, what happens in the alveoli? There's increasing amounts of air trapping both within the alveoli and in the thoracic space. So the patient must now generate a very positive pleural pressure with forced exhalation to try to create a pressure gradient for air to flow out. So as we now think about the transmural pressure, especially at this point right here, which you could think of as slightly proximal to that area of obstruction, there the pressure in the airway is still relatively normal, say at plus 2, proximal to the obstruction. But now the patient has generated a very positive intrathoracic pressure, especially if there's forced exhalation as a component of it. And now you have a very negative transmural pressure right at this point, proximal to the obstruction, and you get further dynamic collapse on exhalation and expiratory flow limitation. And we can see that nicely here on spirometry. Again, here's the normal circumstance here. Exhalation up above, inspiration down below. I've got a patient with significant lower airway obstruction. There may be even a limit on inspiration of the flow that can be achieved. But the classic finding is this expiratory flow limitation where this flattening or scooped out appearance of the expiratory portion of the flow volume loop. And you see that that can get better after you treat it, for example, with, let's say, a bronchodilator in this circumstance of asthma. We can also see evidence of lower airway obstruction on capnography. So if you've got a patient that's intubated, for example, then what we classically see is the lack of a plateau here, lack of an alveolar plateau, because you have lung units with different time constants such that as you are exhaling, lung units with shorter time constants might exhale sooner than lung units with longer time constants. So there is this small, sloped gradual rise in the amount of CO2 that's coming out rather than the same amount of CO2 that's exhaled right when you reach alveolar ventilation on exhalation. So I alluded to the time constant. Well, what is the time constant? The time constant is the time it's required for a system to empty two-thirds of its capacity or down to one-third of its original value. And there's both an inspiratory and expiratory time constant, and it's calculated as the resistance times the compliance. So if the airway resistance is increased, now the time constant is longer. So with significant lower airway obstruction, you see longer time constants. Now, how do you measure the time constant? Well, it's really the inverse of the slope of the flow volume curve during passive deflation. So you need the patient to become passive during exhalation. If they are active during exhalation, the computation of the time constant is much more complicated. And then you can measure the slope of that line of the flow volume curve. And here's an illustrative example of, let's say, a 5-kilo infant that's healthy that has more restrictive disease like ARDS or has lower airway obstruction, let's say, from bronchiolitis, and the aberrancies that you may see in the time constants, and therefore how that might relate to the rate that you may be able to choose on the ventilator, especially if the patient is paralyzed and passive. So under healthy circumstances here, you see the resistance and the compliance are both normal, yielding a sort of normal age-appropriate respiratory rate. So what happens in ARDS? The resistance is relatively normal, but the compliance is severely impaired. That results in a very short time constant and allows you to use a very fast rate, for example, even in a passive patient with ARDS. Patient with lower airway obstruction, the opposite is true. Resistance is severely increased. Compliance may be slightly impaired, especially if there's air trapping, resulting in a very long time constant, and hence needing to use a relatively low respiratory rate, especially when the patient is passive on the ventilator. Now, to really detect expiratory flow limitation, you need to do a maneuver where you get up to total lung capacity and breathe out. That's what we would do in pulmonary function testing to be able to identify this. Certainly, patients that are ventilated can't do that if they're not able to really cooperate, but you can actually simulate that. If you use a cuffed endotracheal tube, you take them up to plus 40 for close to total lung capacity, and then you expose them to a vacuum that generates very negative pressures at, let's say, minus 40 centimeters in water, and you can recreate forced exhalation really to identify the presence of severe lower airway obstruction. This may be particularly relevant as we're thinking about patients that, let's say, have RSV, and not all RSV is RSV bronchiolitis. There is RSV bronchiolitis, and then there is RSV pneumonia, or more restrictive disease in ARDS. What you see is a difference in the clinical phenotype of those patients that have RSV bronchiolitis, where you see air trapping on chest imaging. If you do look in their bronchioles, you see these areas of inflammation and obstruction within the bronchioles. If you do a passive deflation, you see a lower slope here on the flow volume curve, and if you do a forced deflation, then you have this very classic scooped appearance on the flow volume curve. In contrast, RSV-related ARDS or pneumonia, you've got much more infiltrates on chest imaging. You see lots of inflammation around the bronchioles, but the bronchioles are not narrowed. They're not obstructed. The slope is much greater on passive deflation of the flow volume loop, and if you do a forced deflation maneuver, you see no evidence of airway obstruction or a scooped pattern on exhalation. In fact, this is a nice study that sort of highlights this difference, that you look at the critical patients that, let's say, get intubated for RSV-related disease, that while a lot of them have bronchiolitis, a good number of them actually have more of this restrictive phenotype of an ARDS-type picture, where what we see here is that their compliance is more significantly altered with relatively normal airway resistance. I've alluded to this before, but oftentimes, the way to really diagnose lower airway obstruction is with forced exhalation, because that's how you'll pick up that the patient has flow limitations. If we think about the normal circumstance here, as patients are breathing out, the pleural pressure is slightly negative relative to the pressure even in the alveoli or in the airways, so you maintain a slightly positive transpulmonary or transmural pressure gradient here across the airways. During routine exercise, what happens? We may raise our pleural pressure because we have more forced exhalation during routine exercise, but as long as there's no area of obstruction within that airway, that pressure gets transmitted to the alveolar space and to the airways, and the net effect is still a relatively positive transmural pressure with more positive pressure in the airway compared to the pleural space. Now, if I have this area of obstruction, then what happens? As I generate that more positive pleural pressure for forced exhalation, although the transmural pressure may be maintained at the point here distal to the obstruction, at the point of the obstruction and proximal to the obstruction, now instead I have more dynamic collapse because the pressure in this airway is much more negative compared to the pressure that you see outside of it here in the pleural space. Now, there remains a lot of controversy about what to do with PEEP, for example, when you're mechanically ventilating patients with lower airway obstruction, and what we can see here in circumstances of conditions like COPD, where you have airways that might not be completely normal, that there is often this dynamic collapse of the airway on exhalation, even during passive exhalation under neuromuscular blockade. And when you apply some PEEP to that area, then you, in fact, may eliminate that dynamic collapse on end exhalation. So this certainly happens with conditions like COPD, or perhaps with conditions like bronchiectasis. Whether it happens in asthma is, I think, an area still of controversy, but if you keep the applied PEEP that you applied below the intrinsic PEEP, then you should potentially improve the airway dynamics without compromising and adding more air traffic. But perhaps one of the more important principles as we think about mechanical ventilation of patients with lower airway obstruction is to give them enough time to exhale, especially if they're under neuromuscular blockade. So if they're not under neuromuscular blockade, they can do forced exhalation. They can speed up their exhalation process. But if they are completely passive, then we must ensure that there is enough time for flow to return back to baseline before the next breath is given. If not, then these patients have breaths, have auto PEEP with high amount of volume that may be trapped in there. But as you look at a patient that's got very significant lower airway obstruction, what you'll notice, of course, is that their work of breathing is not limited only to exhalation. It's not just about getting air out. Sometimes it's actually quite hard for them to get the air in. Well, why does that happen, right? Because they become air trapped over time. And as they become air trapped, then the pressure that's in the alveoli is relatively positive compared to atmospheric pressure. They've got this area of obstruction here. As they have to breathe in, what do they have to do, right? To get airflow to come, we have to lower the pressure here in the alveoli below what we see in the atmosphere, below atmospheric pressure. So that patient now has to take this pressure of plus 15, drop it to, let's say, zero in order for airflow to even occur. And that auto PEEP results in a lot of wasted effort at the beginning of inspiration. They have to lower this pressure even to have airflow start to occur. And this might be the benefit of using things like CPAP or even BiPAP for patients with lower airway obstruction. If I can increase the pressure here in the point proximal here to the obstruction so that the patient does not have to go below atmospheric pressure, but simply has to go below the PEEP on the ventilator, for example, then airflow can come more easily. So if I match the level of PEEP that I apply with the intrinsic PEEP that the patient has, now they trigger a breath very easily simply by lowering this pressure to, let's say, 14 as compared to 15, and the breath will occur. And we can see that quite nicely if you put an esophageal catheter in the patient, for example, then what you see is that there is effort here on the esophageal catheter of the patient lowering their pleural pressure, and that effort precedes any changes in airway pressure or flow. And that whole amount of work that's done here is all a function of the intrinsic PEEP, i.e., this is the wasted effort, so to speak, without getting any volume component to it. And this is a study that members of our group did and intubated asthmatic patients using esophageal manometry to measure the pressure rate product, the peak-to-trough change in esophageal pressure times the respiratory rate. This is an objective measure of patient effort of breathing. And what you see here is just an example from two patients is that each patient sort of has this curve where their effort of breathing is highest when there is minimal PEEP or zero PEEP that's applied. And then as PEEP is increased, their effort starts to decrease to a point where if you exceed their intrinsic PEEP, now you may start to decrease their total compliance of the lung and impose increased work of breathing on the patient. So now we're going to move further within the interthoracic space from the airways into the pulmonary parenchyma and talk about specifically more restrictive types of lung disease. Here are the board principles of restrictive disease, understand lung volumes and how these change with disease, understand the concept of work of breathing, lung versus chest wall compliance, understand transpulmonary pressures, and look at the factors that affect the depth and frequency of breathing. So this, of course, is one of the most important curves in respiratory physiology, and this is the relationship between end-expiratory lung volume and both compliance as well as pulmonary vascular resistance. And so what we see is that as end-expiratory lung volume on the x-axis, compliance and resistance on the y-axis here, that as we have low end-expiratory lung volume, right, the compliance of the lung is poorest and the resistance is highest, and as we have very high end-expiratory lung volume approaching total lung capacity, the same is true, very low compliance and much higher resistance, and that the optimal point here occurs at normal functional residual capacity where compliance is best and where pulmonary vascular resistance is lowest. Now, functional residual capacity is often very severely perturbed as we think about the diseases, especially restrictive lung diseases, that we encounter in the intensive care unit. And so it's important to remember how these lung volumes relate to one another as patients are breathing under tidal conditions, that end-expiratory volume hopefully is at normal functional residual capacity. Here, of course, we ask them to take as big of a breath in as they possibly can, demonstrating their inspiratory capacity to get up to total lung capacity. They then breathe out as hard and as fast as they can down to residual volume, and then back again at tidal breathing and functional residual capacity is the sum of these two volumes of residual volume and that expiratory reserve volume. Now, as patients get more disease, right, under normal circumstances, functional residual capacity here represents about 30 to 40% of total lung capacity. Patients with airway obstruction have an increase in both total lung capacity and functional residual capacity, i.e. they're operating at that higher end of an expiratory lung volume, which can, of course, compromise compliance. In contrast, those with restrictive disease have a significant reduction in both total lung capacity as well as functional residual capacity. And the mixed disease patients have a reduction in total lung capacity with relative preservation of functional residual capacity. And this is often why we see patients with more mixed disease, let's look at the patient with, for example, bronchopulmonary dysplasia get into trouble very quickly because they have a relative preservation of functional residual capacity, let's say because of more lower airway obstruction, but their inspiratory reserve volume is relatively compromised. And so as they try to take bigger tidal volume breaths, let's say to account for more respiratory disease, they have limited capacity to be able to do that. Now what's what's so magical about FRC? Well remember, FRC is the natural balance point between the lungs and the thorax, right? So the lungs, if they were operating independently of the thorax, they would collapse. The thoracic cage, if it was operating independent of the lung, it would just continue to expand. And so where those two springs are balanced with one another is functional residual capacity. Now it's important to understand what's happening to all the pressures at functional residual capacity, especially the pressure within the pleural space. So remember, under normal circumstances, right, we're balanced by a total transmural pressure. So if we think about the transmural pressure of the respiratory system, that's the pressure inside, i.e. the alveolar pressure, minus the pressure outside, which is the atmospheric pressure. So both the pressure inside and the pressure outside at end expiration normally are zero, right? Alveolar pressure of zero and atmospheric pressure of zero. But in fact, there are two transmural pressures that are balanced. There's the pressure that goes from the alveoli to the pleural space, that's called the transpulmonary pressure, which is slightly positive at end expiration. My alveolar pressure is zero, my pleural pressure is slightly negative, minus five, so zero minus minus five yields a slightly positive transpulmonary pressure at end exhalation, and that's why the alveoli don't collapse. In contrast, across the chest wall, the transmural pressure across the chest wall is slightly negative. Pleural pressure is slightly negative at minus five, minus atmospheric pressure of zero, i.e. minus five. So these two pressures, the transmural pressure across the chest wall and the transpulmonary pressure, balance each other out to have a net balanced trans-respiratory system pressure at end exhalation. And that concept is just further illustrated here, right? These three pressures, the pressure across the respiratory system, alveolar pressure minus atmospheric pressure, pressure across the chest wall, pleural pressure minus atmospheric pressure, and then transpulmonary pressure, which is alveolar pressure minus pleural pressure. Remember, always the pressure inside minus the pressure outside. And as we think back to Boyle's Law, right, now how do we inflate the thorax or the respiratory system? Well, again, now this is a function of that transmural pressure across the system, that as that transmural pressure begins to increase, that's how we start to have an increase in volume. And that increase in transmural pressure can occur either with spontaneous breathing, with a reduction in pleural pressure relative to alveolar pressure, or positive pressure ventilation with an increase in alveolar pressure relative to pleural pressure to generate inflation of the lung. Now remember, the chest wall and the lung have their own mechanical properties. And when they're put together, that's how we generate this compliance curve of the overall respiratory system. That as we think about the lungs themselves, at their unstressed volume, they would be fully deflated here with no volume and no pressure in the system. As we increase the pressure, the volume in the lungs start to increase. In contrast, the chest wall, its unstressed volume, i.e. where the pressure is zero, in fact, is at a relatively high volume. It has that tendency to expand. We put those two together, right, and that's where we see this relationship of the total respiratory system pressure volume relationship, both for negative pressure and for positive pressure. And now as we look at the overall compliance there of the respiratory system, although you can certainly do this directly for the lung, right, how do we determine that based upon these pressure volume relationships? Well, it's primarily determined based upon the slope of this line, right? Remember, compliance is the change in volume over the change in pressure. So as I have the normal lung here, maybe my dynamic relationship on inspiration and on exhalation, and now as the compliance of that lung decreases, now it takes much more pressure to generate anywhere near that same amount of volume during inspiration. This relates to the concept that I spoke about in the other ARDS talk, which is that as we're now trying to ventilate patients with restrictive disease, this pressure volume relationship becomes crucially important because we're trying to ventilate patients in this zone of optimal compliance. This is the quasi-static pressure volume curve here, which demonstrates that as the lung is collapsed, right, the compliance is very poor. If I overcome that area of collapse, I'm in a zone of good compliance, but then if I over distend and I use too high of a volume, for example, now I may get to a point again where I have poor compliance. So we try to maintain our ventilation strategy in the zone of optimal compliance above the lower inflection point, yet below the upper inflection point. We stay above the lower inflection point by applying PEEP. We stay below the upper inflection point by limiting the tidal volume or pressure that we apply. Now an important point to remember as we think specifically about that lower inflection point is the closing volume, or sometimes called the closing capacity, of the alveoli. Under normal circumstances, that closing volume lies between functional residual capacity and residual volume. That at residual volume, most of the alveoli would be collapsed. As you go from residual volume up to functional residual capacity, most of your alveoli, if not all of your alveoli, will open depending on age. And if you sit at functional residual capacity, you are above that closing volume, i.e. most of your alveoli are open. However, there are important age-dependent differences in that relationship between functional residual capacity and closing volume, which highlight why infants in particular are more prone to problems with atelectasis, as an example. So on this graph, we have age and years. This is functional residual capacity minus closing volume. And of course, we want a high value to indicate that there's space between where you're sitting at end expiration and, you know, where the alveoli will collapse. And you see that that relationship is a clear age dependence. As you get older, right, then in fact many lung units may be collapsed, even at normal functional residual capacity. And as you get younger, that same concept is true, that the youngest of patients, in fact, may have many lung units that are collapsed, even at normal functional residual capacity. Now interestingly, the relationship between PaO2 parallels this relationship between functional residual capacity and closing volume, and that PaO2 is also age-dependent, i.e., the AA gradient, in fact, is larger in younger kids and infants as it would be, you know, in an adult. And so you see here that the PaO2 is highest in, you know, in our 20s. That's why we all did so well when we were in our 20s. And as you get older, the PaO2 starts to fall. And as you are younger, the PaO2 also falls, matches that relationship. Now this gets further compounded in infants because not only do they have, you know, a closing volume that is closer to functional residual capacity, but they lack collateral sources of ventilation, such that if they develop this area of atelectasis, here's an example of something called the pores of cone, then an adult might be able to keep that alveoli open with collateral ventilation from adjacent alveoli. In contrast, infants really lack these mechanisms and hence are much more prone to develop atelectasis. So what do we see when a patient develops restrictive disease and impairment in functional residual capacity? Well, often what we see when we're looking at that patient is that they develop increases in their work of breathing. And when we think about work, there's two components of work. There's elastic work and there's resistive work. We think about the elastic work that the lung does. It's based upon this compliance of the lung relationship, i.e. volume on this axis, pressure on this axis. They start at functional residual capacity, do their tidal volume breath. The area under this curve represents the elastic work that the lung must do to inflate. So if I have a lung that now develops more impairment in compliance and functional residual capacity, we see that the slope of this line has now changed, right? And functional residual, we may fall and expiratory lung volume may fall to a lower level. If that patient is trying to generate, let's say, the same volume, now the work that's required to do that is substantially increased. So what do we do as a first next step? Oftentimes we may apply PEEP, right? We apply PEEP. We may recruit some of that lung that hopefully increases that end expiratory lung volume and it makes this area slightly less so that the patient has to do less work in order to move that same volume. And now the work that's created has really two components, right? There's a component based upon the elastic work and then there's a component based upon flow-resistant work. And that work, remember, is the force times the distance. And we can think about work of breathing as the change in pressure times a change in volume. The way it's represented is the area that you see under this curve, right? So under normal circumstances, here's that pressure-volume relationship. So just, you know, to orient you, this is pleural pressure on this axis. It's flipped from the way that the curve was drawn in the last slide just to make the drawings all look very similar. And so here's the normal circumstance that as I lower my pleural pressure slightly, I get a concomitant rise in tidal volume. And the work is sort of nicely represented here by this dynamic pressure-volume curve as the area here under this curve, okay? What happens with restrictive disease? With restrictive disease, now the compliance of the lung is a lot worse. So the slope of this line becomes a lot larger. And so you see this area is increased, okay, largely because of a more negative pleural pressure here to achieve this. In contrast, when you have increases in airway resistance, right, what you see is that there is a sort of wider gap here between the volume and pressure relationship, especially as the patient tries to take the breath in. What you may see is, right, there's no concomitant increase in volume or flow, especially as there's increase or as a drop in pleural pressure. This is the intrinsic PEEP-related problem. Then because of that increased airway resistance, you may have relatively larger decrease in pressure relative to the amount of volume change that happens, i.e. some of that flow that's created is not resulting in a large change in volume. And then there is also expiratory work that you see, especially with this overshooting of that pleural pressure as the patient is doing forced exhalation. And this can be further capitulated here on this graph, which looks at the dynamic pressure-volume curve. You see there are many different components of work. There's the elastic work, right, to inflate the lung. This is the surface tension and fibers of the lung parenchyma and airways. There is the non-elastic work that's related to inspiratory flow and airway resistance. You see here on inspiration, and if you have very high increase in airway resistance, this curve will start to go out like this. And then there may even be some expiratory work that you see related to obstructive lung disease. Another way to understand this conceptually is to look at the difference between static versus dynamic conditions. Static conditions imply that there is no flow that's occurring. So what we measure during static conditions is really reflective of the elastic work on the system, the elastic properties of the system, i.e. what's required to simply inflate the lung, the pressure and volume there. In contrast, under dynamic conditions, this includes both what's required to inflate the lung, but also the components that relate to airway resistance. So here's our static pressure-volume curve. You can think of this as the driving pressure, i.e. the plateau pressure minus the PEEP, to compute the static compliance, tidal volume divided by driving pressure, plateau pressure minus PEEP. In contrast, the dynamic compliance incorporates both resistive and elastic components, i.e. we have the delta pressure on the denominator, which is the peak inspiratory pressure minus the PEEP. And that difference between the peak inspiratory pressure and the plateau pressure is what reflects the pressure gradient that's required for airflow to occur, i.e. the resistive component. Now this can all get put together with something that's called the Campbell diagram. The Campbell diagram reflects all different components, flow resistive component, elastic component, and then potentially some imposed work which may occur from either something like the breathing apparatus, i.e. like the endotracheal tube, although the extent to which that happens is a is an area of controversy. So here is the elastic work, the work that's required really to inflate the lung. Here is the flow resistive work. This is, you know, the work that's normal work during inspiration and exhalation that's required from the airway resistance, and then potentially imposed work that may come from a breathing apparatus. And this difference between elastic and resistive work is also really important as we try to understand breathing patterns of patients, right, as they have either restrictive or obstructive disease. So as we think about the relationship between respiratory rate, which is on this x-axis, and work of breathing, which is on the y-axis, remember that total work is the sum of the work related to resistance and the sum related to elastance. So under normal circumstances you have this u-shaped curve where the compromise between airway resistive work and elastic work is optimal around a respiratory rate of 15. As you increase the respiratory rate, right, there will be more flow resistance related work because you're having to overcome the resistance of the upper airway many times. In contrast, if you want to think about the elastic work, then the elastic work is highest when the breath frequency is lowest because you need to move a bigger tidal volume to maintain that same minute ventilation. So if I have a disease state that has increased elastic work, i.e. poor pulmonary compliance, this gets shifted up and to the right. The airflow work is the same, the elastic work is increased, and that's why patients with more parenchymal disease breathe generally with the faster respiratory rate and a lower tidal volume because it's more efficient for them to do that since the elastic work is increased so much. In contrast, where resistive work is increased, now we're shifted up and to the left, and so those patients prefer to breathe at a relatively lower respiratory rate so they don't have to overcome that airy resistance as frequently. And this concept of work of breathing becomes really important as we think about total energy utilization when patients have significant respiratory disease because in health, it's only a very small percent of total body energy expenditure, but in extreme situations of respiratory disease, this can increase by as much as 50-fold. Now remember, we've been talking mostly about the overall work of the respiratory system, and there are really two components there. There's a chest wall component as well as the lung component, and sometimes we have circumstances like this, and even babies that have very significant impairments in their chest wall compliance. But as I think about injury to the lung, what's most important for injury to the lung is the transpulmonary pressure, that is the pressure across the alveoli. Remember, the transpulmonary pressure is equal to my alveolar pressure minus the pleural pressure. Under normal circumstances, we can estimate these that the alveolar pressure is reflected as the airway pressure, especially during static conditions, and that the pleural pressure is, as a surrogate, could be the esophageal pressure, so we often we can place this esophageal catheter to estimate that pleural pressure. And here's a normal waveform that we may see with the airway pressure here, an esophageal pressure on a passive patient here where the esophageal pressure goes up just slightly during inspiration, and then the subtraction of those two to generate the transpulmonary pressure. And one of the important applications is to think about the transpulmonary pressure at end exhalation, and this might be helpful for us to guide PEEP titration. So remember at end exhalation, normally we have a slightly positive transpulmonary pressure, alveolar pressure is zero, the pleural pressure is slightly negative, resulting in a slightly positive transpulmonary pressure. So what happens if I have somebody that has increases in pleural pressure, let's say from obesity, so now instead of this being a negative number, right, the pleural pressure, the pleural pressure is now positive, resulting in a net negative transpulmonary pressure, which will promote collapse of that alveoli at end expiration. So what can we do? Well this is where the application of PEEP might be helpful to overcome the increases in pleural pressure. So here's a chamber that is simulating pleural pressure in the bag that is the alveoli, and what you see is that these small things here, the chamber pressure is going up from 6 to 12 to 20, but you can keep that alveoli inflated by applying PEEP at that same amount to keep the total transmural pressure or the transpulmonary pressure relatively neutral. So the other area that's relevant as we think about transpulmonary pressure is the transpulmonary pressure at the end of inspiration, and this is a marker of stress on the lung. So here's a five-year-old obese girl who's got a body mass index of, let's say, 40. Peak pressure is 26, plateau pressure is 23, so if I measure the total driving pressure, right, this would be 23 minus the PEEP, which is measured at eight and a half, so the total driving pressure is 14 and a half centimeters of water. Now that girl has significant impairment in her chest wall mechanics, right, so she has an elevated, relatively elevated pleural pressure, and some of the pressure that we apply at the airway is actually being used to move her chest wall out of the way to allow the tidal volume to occur. So as we see here, her end esophageal pressure during that inspiratory hold is 13 and a half, so we can calculate the transpulmonary driving pressure or the transpulmonary plateau pressure, where we subtract off this plateau, we take this main plateau pressure minus the end esophageal plateau pressure, and so what you see is the transpulmonary pressure at end inspiration is a relatively smaller amount of nine and a half. So the way you can think about this conceptually is that almost, you know, four centimeters of water of this driving pressure that we're applying here is actually being used to move the chest wall out of the way. Now the last section that we'll talk about relates to disorders of the respiratory muscles, and remember, of course, our most important respiratory muscle that we're most dependent upon is the diaphragm. The diaphragm has this dome shape, it contracts downward, that results in the movement in a lateral direction of the ribcage, increasing the transverse diameter of the thorax to allow for expansion. And remember, the diaphragm is comprised of both type 1 and type 2 muscle fibers, and there are important differences between that in infants as compared to adults. The proportion of type 1 muscle fibers increases with age and really doesn't plateau to adult levels until after about two years of age, which is what makes infants in particular very susceptible to diseases of the diaphragm. And certainly one of the things we see quite commonly is the development of diaphragmatic weakness for patients that are on mechanical ventilation, and this is, you know, an adult study that uses diaphragm ultrasound to highlight that 30 to 40 percent of mechanically ventilated adults develop significant atrophy of the diaphragm really within the first couple days of mechanical ventilation, and one of the major risk factors for it is the amount of contraction that the diaphragm is doing during mechanical ventilation. If you can keep a physiologic level of diaphragmatic contraction, then for many of these patients you can prevent that weakness from developing and they keep a normal amount of diaphragmatic structure. And the biggest, one of the biggest risk factors is of course lack of use of the diaphragm, i.e. things like use of neuromuscular blockade or no respiratory activity. Now when the diaphragm is not able to do enough work, then we often recruit these accessory muscles. Accessory muscles of inspiration include the external intercostals, like the scalenes, which elevate the first two ribs, or the sternocleidomastoid, which helps raise the sternum. Or especially in circumstances of lower airway obstruction, we recruit muscles, accessory muscles, for exhalation, like the abdominal wall muscles or the internal intercostal muscles. And what happens with intercostal muscle weakness, let's say somebody gets transverse myelitis, for example, or a spinal cord injury, now you have a lack of stability of the chest wall. So that when the diaphragm contracts, the diaphragm contracts downward and normally we would have this expansion of the thorax and the chest wall. You in fact have more of a collapse now of the thorax and the chest wall, which leads to significant asynchrony. And in fact we can measure this asynchrony in clinical practice with respiratory inductance plethysmography. This is the same technique that's used for sleep studies, for example, to detect, you know, things like upper airway obstruction and obstructive sleep apnea. There's a band around the ribcage and around the abdomen, and what you would see normally is that the ribcage and the abdomen are entirely in phase with their breathing. That is, as the abdomen contracts, the diaphragm contracts, the ribcage follows almost immediately there afterwards, and there are these sort of perfectly aligned sine waves, which results in a minimal difference in the phase, i.e. between the peaks of these two they're perfectly aligned. As patients start to have more respiratory effort and they recruit their accessory muscles, now there starts to become a bit of a phase shift between the abdomen and the ribcage, but you'll see that they're still generally going in the same direction. But what can happen if you have either abdominal or ribcage paralysis or very severe weakness is now the abdomen and the ribcage are nearly up in opposite directions of one another, i.e. they're almost 180 degrees here out of phase, that when one is at its peak, the other is at its trough. And this paradox between the diaphragm and the chest wall is actually quite common even during normal sleep in neonates, and as you see here during quiet sleep, the neonates are breathing predominantly with their abdomen and their diaphragm, the chest wall is not helping, not hurting that much. As they go into deep REM sleep, then what happens is the chest wall starts to collapse as the diaphragm takes a big breath in, and this relates to chest wall instability in neonates, especially during deep sleep. You can also see a relative difference based upon whether the area of paralysis or weakness is the diaphragm versus, let's say, the intercostal muscles. In this circumstance here, this is a child with botulism that has predominantly diaphragmatic paralysis, and what you see here is actually the ribcage is leading the breath and the abdomen is following, because the direction of this loop goes this way first with ribcage on the y-axis, right, and the abdomen is sucking in. In contrast, this is a child with transverse myelitis, where now the abdomen is still leading the breath, i.e. you're going in a counterclockwise direction like this, but again they're 180 degrees out of phase. So there's the compartment model that I think about for respiratory failure. Hopefully you find it a useful approach and strategy as you're thinking about the different types of respiratory diseases that we encounter in the ICU. All right, so that leads to a couple of questions. Hopefully you were paying attention, and this will test if you were. So the most likely disease process responsible for the condition highlighted to the left, the solid linus disease, is asthma, bronchiolitis, croup, obstructive sleep apnea, or subglottic stenosis. Okay, the answer here is subglottic stenosis. So what do we see? We see a fixed obstruction that is affecting both inspiration with inspiratory flow limitation and exhalation with expiratory flow limitation. So the only disease process here that is a fixed obstruction is subglottic stenosis, which is why that's the correct answer. Okay, a four-year-old girl presents with a one-day history of difficulty breathing, wheezing, accessory muscle use, prolonged exhalation, and a mild lactic acidosis. Her oxygen saturation of room air is 100%. She's given bronchodilators and steroids placed on CPAP of 8 by a face mask with 35% FiO2 with a significant reduction in her work of breathing. The most important mechanism of action of CPAP to lower work of breathing in this circumstance is likely related to improving pulmonary compliance, one. Two, increasing end expiratory lung volume to make it closer to normal FRC. Three, improving oxygen delivery to the respiratory muscles. Four, decreasing the difference between airway and alveolar pressure. Five, improving laminar flow. Okay, so the correct answer here is number four, decreasing the difference between alveolar airway pressure and alveolar pressure. So this is the concept of intrinsic PEEP and increased work of breathing that patients with lower airway obstruction have because of intrinsic PEEP and needing to overcome that intrinsic PEEP in order to have airflow occur. So by applying PEEP here to more closely match what the patient's intrinsic PEEP is, you decrease the inspiratory work. You likely are not improving pulmonary compliance. These patients are often air trapped and they're at the high end of an expiratory lung volume, and that's why number two is also not the right answer. Laminar flow, there might be some improvement in laminar flow with the use of CPAP, but that's probably more relevant with bronchodilator drugs or even the use of heliox, etc. And oxygen delivery of the respiratory muscles might be slightly improved with this, but that's not really the primary mechanism for this patient to have significant increases in work of breathing. So infants may be more prone to develop hypoxemic respiratory failure than young adults for all of the following reasons except lower baseline PaO2, relative lack of collateral sources of ventilation, critical closing capacity closer to functional residual capacity, increased elastic recoil of the chest wall, or more horizontal orientation of the ribs. Okay, so the correct answer here, this is an except, is four. So four is not a true statement. It is decreased elastic recoil of the chest wall. All the others are true statements. The lower baseline PaO2 relates to the fact that critical closing capacity is closer to FRC, so they have relatively more analectasis even at normal end exhalation. They also lack those collateral sources of ventilation and do have a more horizontal orientation of the ribs, which puts them at a bit of a mechanical disadvantage.

respiratory mechanics

monitoring

pediatric critical care

lower respiratory tract infections

compartment-based approach

airway obstruction

transmural pressure

lung volumes

respiratory muscle weakness