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Good afternoon. Um, yet again, I'm Doctor John Bogle, Uh, recently retired consultant. Any quest consultant, intensive care, medicine and anaesthetics. And I want to carry on talking to you today about some of the physiological principles that underpin the way we approach and treat patients' and the common theme, um, has been delivery of oxygen, which is our ultimate goal and how we can improve. Um, one of the aspects of this, which is cardiac output through hemodynamics. And we're using fluid. This is probably the commonest thing you'll be doing. So, um oops. So we're trying today to try and understand some of the basic physiology underpinning some of this and surprisingly, um, poorly taught and poorly, I think poorly taught, often not taught and poorly understood. So hopefully today you'll have an understanding of how this works and some clinical scenarios as to where you can use this. Okay, so we go back to the same paradigm that we talked about in the very first lecture, and that was the ultimate goal of what we're trying to do, especially in a chaotic situation like trauma is you get a lot of, um, a lot of information a lot of requests. You know, pest tubes, intubate, blood, whatever. You just want to have somebody stepping back and just, you know, accusing the strategy. And the strategy is we've got to improve oxygen delivery. And to do that, we need three factors. Cardiac output, hemoglobin and saturate. So that's a good way to to put some order to the chaos. And each of these factors, as I said before, can be broken down to their sub factors. Won't go reading them all to you. But you can see they all make sense and those sub factors can be broken into their sub sub factors. And again, you don't have to read them all. But it's basically the more confused things are, the more chaotic. You want to skip the details, you can work them out later and go right back to the top of those three factors. And if they're okay, you're okay. And today we're going to talk about, uh, what I think is the most important of the three factors, which is cardiac output. And the thing that you most commonly do to improve that is preload. You're gonna fill the heart. That's the commonest thing you're going to do other things will be done. But that's the commonest and we have to. We really have to understand how this works and why it works. Okay, so this is a kind of typical clinical case. I used to get these all the time when I was in intensive care. So a 63 year old woman true story this and could have been sick for three days with nausea, vomiting, diarrhea. So she's lost a lot of fluid. She came to the excellent emergency department on a Thursday afternoon at 4 30. Her BP was lower. Heart rate was fast, her yard up. It was poor and her lactate was high. The doctors who took care of her gave her almost 10 liters of crystalloid, so ringers liked it. After that, her blood picture hardly came up at all. Her heart rate went a little bit faster. Urine output was worse. And most importantly, her lactate went up not down up. So next morning on Friday at 7. 30 I was in the intensive care unit with, uh with our registrar, and we received a phone call and they asked, Can you take this lady and we said yes, of course. And I turned to my registrar, and I said, within an hour, she'll be dead, and I was wrong. 20 minutes later, she had a cardiac arrest and died. And the question is, what were the two things that went wrong? Can anybody quickly tell me what? The two things that might have gone wrong? We're or write them down and let me know. Okay. Well, we don't have a lot of time, sadly, but the two things Sorry, are you able to see the chat? Would you like me to read out the response? If you could read them out for me, please. I can't see them chat. So someone wrote BP and heart rate? Well, yes and no. I mean, these were things that were not adequate and had to be treated. The two things that were done that were wrong was one to give her some fluid was reasonable, but to 10 liters of fluid. She was not responding to this, and that was way too much fluid. Secondly, they should have when they tried a reasonable amount of fluid, say a couple of leaders. If they saw they weren't going to improve. They could have called the intensive care unit, where we have more invasive forms of monitoring or even locally. If they had, you know, a better form of monitoring and they'd see that this woman was probably not fluid responsive. And we'll see what I'm talking about here in a second so that a they should have not used 10 liters. That's way too much. They're wasting time, and they're just going to drown the poor woman. And he's not because he's not responding to fluid by improving your cardiac output. Okay, so what are we trying to treat your from the theoretical point of view? This is the starling curve that everybody talks about on the X axis is the filling of the ventricle that could be measured as pressure because we often don't know what filling is. We have to look at pressure that could be right, right? Atrial pressure or, more common, we talk about the CBP central venous pressure, and on the Y axis is the cardiac output. And as you can see, there's a steep part of this curve and there's a flat part to this curve. Now everybody who's listening to this, I presume. And I hope I'm the same are on the steep part of this curve. That means that if you give me fluid, I will increase my cardiac output. Okay? And I'll get towards the flat part of the curve now because I will improve cardiac output Does not mean you have to give me fluid. I'm fine. I feel healthy. But I was sick as this woman was. You want to know, Where is she? On this curve. And so the first thing would have been reasonable to do is get fluid and see if you can optimize the filling so increased cardiac output by giving fluid with with some filling of the ventricle. If that was not enough, if he was not responding, that means because on the flat part of that curve, then you're gonna have to do something about that. There's no point in keep filling. Keep you on filling because all you're going to do is get no more cardiac output, very minimal. But you're going to increase the pressure that's going to go. The foods gonna go into your lungs, and so you want to alter that curve. And what do you do when you get to the top of the starting curve, you then think about using inotropes. So you're getting a different curve. You're getting a better curve. If you like. You're getting more output for the same feeling. Okay, so first you want to maximize the cardiac filling. And that's what we're doing, basically stretching the cardiac muscles. So we're maximizing stretch. And secondly, if the cardiac output is still inadequate, as it wasn't this lady, then you want to try and improve energetics with inotropes. Now, if they had contacted us early, we would have taken her. We'd have used hemodynamic monitors and we'd be able to determine exactly where she was on the curve and then realized that she's not going to respond to Fluid because she's on the flat part of the curve. We had given her inotropes and hopefully improve your cardiac output. I can't guarantee her to survive, but she would have a better chance. So this selectors know about the stretching of the heart muscle, the optimizing, the stretching. So we're talking about filling basically, so we're going to try and understand some of the physiology of preload. So I do apologize that some of My analogies are a bit simplistic, but people do remember. So what is this bag of leftists have to do with starlings? Lot of the heart. So I, um I spend a lot of my times in the mountains. I used to be a fairly keen mountaineer, and I have a small apartment in the French Alps and I have to go down to the valley to get my food. And one day I was filling my car with groceries and, uh, the supermarkets at 807 m. And so I took a photograph of this bag of lettuces. My son was asking me what I was doing, and I said, I'm getting ready for a lecture and he couldn't understand what I was talking about. Anyway, that's the size of the bag of prewashed. Let this you put it in the boot of your car and I was driving home. So where's home? Home is there. And that's a friend of mine, to friends of mine and myself on this client. So we're going to talk about something that's very important to understand. It's transmural pressure now if you go to our place and it's at 1424 m. So we open the boot of the car when we got home, and now the bag looks like this. It's massive. Why? Because the pressure inside the bag hasn't changed. It's the pressure outside has dropped because we're at a higher altitude. So the pressure inside compared to outside has gotten bigger. So it's transmural pressure. Talk about not the absolute pressure inside the bag. It's the difference between the pressure inside the bag and outside, and the outside has dropped, so there's an increase in transmural pressure. Hence, the bag is stretched, and what we're talking about here is to do with Stark. Amir's Sockem ears are making up the cardiac muscle, and you have acting and mycin. And as you stretch the heart, you're pulling those acting fibers apart, which are overlapping. And so the linking is sort of blocked out by the overlap, uh, fiber. So as you see as you pull them apart, they have more exposure and hence more linkups and hence a stronger contraction until you get to the maximum point where there's no more overlap. And there's no point in stretch community further because you're not going to get a stronger contraction. So it's all about the stretch of eventual during diastolic because you want to reduce the overlap of the active mice and cross briquettes. So how did Starling do this? Well, this is an old old experiment. He wanted to know if by stretching the heart by filling it if you got a greater cardiac output. Now, in 1914, when Starling was working, he couldn't use isotopes to measure the volume of the heart. He didn't have echo. So what he did was he put the heart in a glass. They are basically in a bathtub called the bells Cardiology er And what that does is if you put yourself in a bathtub that's full to the brim with water, the water that's displaced, we'll tell you what your volume is. And so as the volume was displaced by the heart, that got bigger and smaller as he filled it and let it empty, he had it connected to a smoke drum and you could see the volume. So he had, uh, he knew what the filling was by measuring the overspill of the water. So that's Archimedes Principal, and you could measure the CDP so it can relate the two. And then he found that as one went up, the other one went up. But this heart and this experiment as a dog heart was exposed to atmospheric pressure. So that was totally different to what happens with us. So what Starling was really saying, If you look at it from a conceptual point of view, as we just talked about as you stretch the heart by filling it, you reduce the overlap of the acting fibers and you get a stronger link up between acting, um, eyes in and you get a stronger cardiac output. Strong more work from your heart muscle. Then you get to the top. So all the fibers are now maximally uh, pulled apart. There's no more overlap, and if you keep filling it, you're not going to get any more increase in stroke work or cardiac output. The heart can't work any harder. It's already maximized, and so all you're going to do is just increase the pressure as you feel it more and more. And that's not good. So you're trying to get to the talk of your starling curve. Now let's look at intrathoracic pressure because our hearts are within our thorax. They're not like a dog's heart in starlings experiment, They're not exposed to atmosphere. Your heart is within your thorax. So when you breathe normally and here's a question for you. When I breathe in normally I breathe out and then I breathe in and breathe out what sort of pressures are in my thorax that are surrounding my heart. Anybody want to take a guess? What? The pressures are breathing out and breathing in, breathing out, breathing in anybody. There are no responses in the chat, so Okay, All right. So if you look at them normally as you breathe out, you expire. Your pressure is zero. When you breathe in, it's about minus three, minus four minus five. You're sucking air into your thorax pipe. Construct contracting your diaphragm and increasing your your intercostal muscles. Your chest expands. So you're not talking about big pressure, sort zero to minus five. If you yawn because this lecture is boring you you might go down to minus eight. If you give a cough might be plus 10. So those are the kind of pressures that surround your heart normally. Now think about this when you ventilate somebody who's sick and you suddenly turn the ventilator on you're gonna use plus five plus 10 plus 20 or more centimeters of water. So this is something that's totally unfit, geological, something that's very, very, um, bizarre for the heart. Your heart's not used to being squeezed like that because it's being squeezed by that high pressure. And that was one of the problems. When you put someone on a ventilator, there are consequences, and they're very important. So you don't ventilate someone unless you really have a good reason to. And that was one of the first lessons they've learned with Covid, by the way. So, yes, you ventilate somebody if you have to, but you don't just do it automatically because there are physiological consequences. So what if I take a a trumpet? I'm a trumpet player, and I decide I'm going to really blow hard on my trumpet. And uh, that's called the valsalva maneuver. If I do that long enough, I will pass out. So what is So what is the maximum pressure that I can generate if I'm blowing hard on a trumpet? Or if I bear down well, if you look at this. This is Louis Armstrong, the famous jazz trumpeter, And someone actually did a PhD on this, and they found that the maximum inter thoracic pressure was 157 years of water. So we're going from normally zero to minus 2345 to suddenly plus 1 50. Then you can imagine that has some pretty serious physiological consequences. So what would they be? Well, first, you have to understand what happens when you squeeze the heart. And when I say squeeze the heart, I mean that you're bearing down with this valsalva maneuver. So it's like you're really squeezing. If you take a syringe full of air and you cap the end of it and you try and compress it, you can compress it. It's compressible. It's got compliance. Okay, you won't. You'll get an increasing pressure. But it will be, you know, somewhat, uh, minimized. But you can compress that air if you take that same syringe instead of filling it with air. You fill it with fluid water in this case, but it could be the heart that would be full of blood. And you try and compress it. You can't compress it. It's non compressible, and so you're going to get just an increase. Massive increase in pressure, not volume change, but so it's very, very poor compliance. So lots of pressure, but very little of any volume change, so your heart, if you think about it, it's not hopefully not full of air. It's full of fluid blood. So if you squeeze it, all it'll do is increase the pressure. So let's look at this cartoon. Now. You have to understand something. When you measure a pressure anywhere in the body, you're always going to have to compare it to something else. So, for example, if I say my BP see, I put a cannula into my radial artery and I want to know what my BP is. And I have a monitor set up and it says the systolic pressure is 1 20 diastolic 81 2081 2080. What we're saying is it's 100 and 20 millimeters of mercury compared to atmosphere. Okay, so the first thing you do when you're using a monitor, you have 20 it by opening the monitor to atmosphere. So it knows zero is atmosphere and then if it says 1 20 it means it's 1 20 relative to atmosphere. So if I put a catheter into a central venous catheter into my internal curricular vein, for example, which is a very common procedure, Um, and I measure the CVP in my heart and it says, say, five, the normal values between zero and five. Let's say if it says five and if I'm my normal intrathoracic pressure is zero. We just said it's zero of minus three. Normally, then what is the transmural pressure that the standing pressure of my heart well plus five inside, zero outside. It's plus five now What if I were to bear down like that trumpet player and I would create a pressure inside of 1 50 because my heart started off us plus five? And as I squeeze just like the syringe, I squeeze the heart. The 1 50 will be transmitted to the inside of the heart, just like the syringe were full of water, and I'm starting off with plus five. So 1 50 plus five is 1 55. So if I measure the c d. P compared to atmosphere, you'll see a CBP of 1 55. Now you'll think you may be thinking, Wow, my heart's going to explode 1 55. That's massive. And you can see this in some clinical scenarios, like a pericardial effusion or attention pneumothorax. You'll see people with pericardial Sorry, not infusion tamponade. You'll see people with very, very high C VPs. And yet what is the distending pressure of the heart? In this example? It's plus five the same. So looking at a C P on its own won't necessarily give you an idea of what the feeling is, because in both of these cases, the filling is the same and sense of the stretch of the heart. The reason is that you have a high, uh, intrathoracic pressure. And by the way, if you don't believe this, go into a mirror in your bathroom, put your thumb in your mouth and blow as hard as you can, and you look at the neck veins in your neck and we'll stand out because you're raising your C D. P. Because you're squeezing your heart with this high intrathoracic pressure. So this stunning pressure of the heart is exactly the same. The bags of lettuce are the same transmural pressures. Now you may. This is the first cartoon again. Now what you may not know is the I said the maximum filling pressure. Sorry, the maximum intrathoracic pressure if you blow hard, that's called a valsalva maneuver is about 1 50 or so, depending on how fit you are. On the other hand, you can do something that's the opposite of that. That's called a Mueller maneuver, and that's you're basically trying to suck as hard as you can, so you're creating as much negative pressure as you can. So, for example, if someone has a tracheostomy and I remember seeing this, uh, not that long ago someone's tracheostomy was they were breathing on a tracheostomy, and suddenly they were struggling to breathe, and the nursing staff were pretty more and more oxygen on. I said, No, no, there's a problem here, and I took the tracheostomy tube out because they were really struggling. And then I put in an endotracheal tube from the mouth to liberate the passage into his lungs. And what happened was that the extreme negative pressure by you know it's basically sucking really hard. Now, the maximum you can generate as a negative pressure is you give the order of 100 centimeters of water. So a valsalva and they were bearing down is about 1 50. And this is all these are rough numbers, but the most negative pressure you can generate. If you're blocked off your larynx or you block off your bronchial tube, you're under to kill two. Bir, your tracheostomy tube is about minus 100 minus. Not plus. And so, um, what happened in the case with this tracheostomy? As soon as I put the new tube in, suddenly, masses of pink champagne came out of the tube. In other words, masses of red stained pulmonary edema. And the question is why? Well, this is why? Because in this case, uh, going back to our cartoon if you're starting off of plus five inside the heart and you're creating a minus 100 outside the heart, transmural pressure will be my +1055 to start with and you're making it negative by 100. That's +105. So now you got your bag of lettuces because it's being taken to an atmosphere that's got a lower pressure outside it. Now you'd say, Wow, your heart's going to explode in this case. Well, your heart's thick walled muscle. It won't explode, but you may get what we call negative pressure pulmonary edema. And how does that work? Well, your heart is very thick walls, so we can't expand explode. But there are a lot of very fragile pulmonary blood vessels in your thorax, and they are exposed to distending pressure as you can see there and they are going to crack open. And there you can see a very good electron micrograph of the capillary being stretched apart. And there's your alveolus. And of course, because the this it's disrupt the capillaries, disrupted a dumb A fluid and red cells will pour into the alveolus. And then you're gonna get this massive outpouring of negative pressure pulmonary edema. But I feel I call the pink champagne. It's very dramatic. It's very dramatic, and it looks like this. You get a massive, batwing hungry edema that's purely due to the negative pressure. And by the way, we wrote an article about this case and there were several cases I've seen. And the treatment, as they say in the books, is wrong. It's not diuretics. It's not because you have too much fluid on board. What you want to use is CPAP. You want to use positive pressure to try and help, uh, squeeze the heart of it. Not not distend the heart by sucking with negative pressure around it. You want a bit of positive pressure around the heart. Okay, so here's a clinical case to give you some relevance to this. So here's a guy who was walking across the street and he, um, he's fractured his femur. He's got a distended abdomen. He's resuscitated in the hospital. He's just arrived in the hospital, and they're starting to give him crystalloids. But he's just starting to be resuscitated. He's in agony because he's fractured his leg. So the nice doctor gives him some morphine. What might happen? And don't say he stops breathing because if you're in pain, you can't stop breathing with morphine. You gotta only morphine only stops breathing if you're not in pain. This pain is a very good stimulant to breathe. Anybody know what might happen? There are no responses in the chart. Okay, Well, you I was assuming you're going to say he might drop crash his BP and that's absolutely true. And the question is, why? Well, that's we're going to explain. So now there's something you have to understand. We're going to get into the sort of the nuts and bolts of venous return the blood coming back into your heart. There's this. There's a concept many, many of you may not have heard of this called mean systemic feeling pressure. Some people also call it mean circulatory pressure. I'm going to stick to mean systemic feeling pressure. M S F P. Now, if, um, this is something that may surprise you And I've done this several times with some of the junior doctors if you have somebody in intensive care and you put a cannula into his into his radio artery so you can see the BP and we have a central line going into his right heart so you can see the CBP And this happened to us not that long ago. The patient was going to die set. We knew that, but we were looking on the screen at the cardiovascular system and what we saw was this is the arterial pressure was going 1 2081 2081 2080 the CBP was going, uh, 2 to 42 to four, bouncing the wall, and then the person's heart stopped as we expected, so they were dead. So the question I want to ask you is, if your dead, What is the pressure going to be in your arterial system? Does anybody know? Someone has said zero. Okay, well, that's that's very reasonable. Everybody would say they're dead, so there's no pressure, right? Well, first thing you have to understand is the pressure. If they're okay, this is a very basic physics concept for you to have flow anywhere on this planet that's got gravity. You have to have high pressure relative to a low pressure. So, uh, a river will run from a mountain lake to the sea. The greater the difference in the high to low pressure, the greater the flow. If you have no gradient and pressure pressure, gradient, if it's zero, you don't get flow, it's a stagnant. So if the heart has stopped, the patient is dead. The pressure in the arterial system will be the same as the pressure in the central venous system will be the same as the pressure in the capillary system, if you can measure it, will be the same as the pressure in the venule system. All the pressures are going to be equal because there's no flow. All right, so what happens now? Here's what it looked like as the person's BP. You see 1, 2081 2080 central venous pressure and when they, when the hardest stopped, there's no flow. All the pressures have equalized because there's no flow. But it's not zero. It's about the order of magnitude of plus 8 to 10. Why? Because the the volume of blood in the vascular system is distending. This elastic coded system, the system is, is got. These walls are I've got elastic fibers, and so they're distending that so there's there's a pressure and that pressure at no flow, which means it's the arterial equals the capillary, the venue, ALS and the main, uh, central veins are all going to be equal, and there's gonna be a pressure of eight. That pressure is what we call the mean systemic feeling pressure, and you'll see how vitally important this is. Okay, so it's the pressure in the vascular is to circuit when there's no flow So what is venous to return? Venous return? As I said, any flow has got to have an upstream and downstream pressure and upstream pressure that's higher than the downstream pressure. If they're equal, there's no flow, and the higher the greater difference in gradient, the more flow there is. So what determines the flow into the venous side of the heart? Other words. Blood coming back to your heart, which is called venous return. It's the difference, in other words, the gradient between the meat steak filling pressure and the C V P. Okay, Now, a lot of people think that the left heart pumps blood all the way around the circuit back to the right heart. And that doesn't work that way. Because, as you can see in this diagram, the systolic pressure is, uh, is the energy that's being generated by the left heart. And most of the energy is dissipated, is used up to get the blood through the very high resistant arterials. It's the arterials that are the great resistance, and they use up a lot of that energy. And so what happens is that, um, your pressure drops dramatically. So what's what's determining your upstream pressure, the mean systemic feeling, pressure, that pressure that's being generated by the elastic recoil of those vessels. And by the way, about 70% of your blood is in those vessels. Very little of it is in the arterial system. Okay, so where is this upstream pressure located? Oh, sorry. And then there's the downstream pressure, which is a C. D. P. And the gradient determines how much flow goes back to the heart. So where's the upstream pressure located? They're way, way down, so it's very, very low. And where's the CBP located? Right there. So the pressure gradient that's going to determine how much blood comes back into your heart is actually very small, and it's determined mainly in the capillaries and the venue ALS as the upstream pressure, the mean systemic feeling pressure and the C V P, which is your downstream pressure. Now, if you recall, I said to you that if you were to do a valsalva maneuver blowing a trump, but long enough, you would pass out. It's because you're raising your cgp by squeezing your heart, you're reducing the gradient and because you're getting less blood coming back to your heart, which pumps less blood to your brain. You pass out and I used to do that when I was a child in the United States. We used to call that fun. That was a game we started. So how does this work? So I'm gonna use again one of my stupid analogies. So let's say I have I assume I don't know if all of you have, but if you ever slept on an air mattress, when you take the air mattress out of its bag and you lay it on the floor, it's completely empty and you're gonna start pumping it full of air. Okay, so that the air you're pumping into air mattress. So inside the air mattress, there's no there's no stretch. There's no someone once used in one of my lectures. They use the term bounciness, and I thought that was really good. So it's not bouncing at all. You couldn't sleep on, so you're gonna start pumping it full of air, and it's totally collapsed. Now, as you fill it with more and more air in this example, you're going to get the air mattress is going to fill up, and it's gonna fill to its maximum capacity, but as soon as it reaches that maximum capacity. If you try to sleep on it, you can't because there's no stretch, there's no bounciness to it, and the pressure inside the air mattress is still zero. So you filled all that air mattress to its maximum capacity. Well, with what we call its maximum unstressed volume. Okay, these are these are important terms unstressed volume so you can't sleep on that air mattress. There's no bounciness to it. You haven't stretched the elastic fibers in the wall of the air mattress. Now, if you keep filling it even more, what you've done is you haven't increased the size of the air mattress. But you've made it a lot bouncier because you're stretching the elastic walls of the air mattress. And so now you've generated pressure inside it, and it can withstand your weight, and now you can sleep on it. And the pressure. The volume you've added to that at maximal, capacity filled air mattress to make it bouncy is what we call the stress volume. So these are two very important terms unstressed and stressed volume. Okay, so let's go back to the guy who was who had a broken leg, so he's lost a couple of liters of blood in his leg in his femur. He had a distended abdomen, so he probably had a ruptured spleen or some sort of catastrophe that had blood in his abdomen. So he's probably very low on fluid. He was just starting to be resuscitated, so it wasn't fully resuscitated. So what happens if you vino dilate? So what we're doing now again, let's go back to the silly analogy of the air mattress. If I could magically make my air mattress bigger or magically make it smaller, I will be converting stressed unstressed Volume vice versa. So let's say I have an air mattress is imagine. It's nice and bouncy. I'm going to sleep on it and some somehow, magically, I can make it twice as big. What's going to happen is that bounciness is going to be lost because a lot of that stress volume now is going to have to fill up the new newly enlarged air mattress to to fill up, and it's going to become unstressed volume. So what happens when you give a drug that vino dilates? You just made your air mattress bigger. And so you're losing that that bounciness. And so you're mean, sustaining filling pressure. Your upstream pressure is going to drop, which means your venous return is going to drop, which means your left heart's going to get less blood coming to it eventually, and which means your BP and cardiac output are going to drop. On the other hand, if I were to give somebody a small dose of a vino constructor, for example, very small dose of your adrenaline, I can make that air mattress suddenly from whatever size it is to say, Let's say from magically make it half the size. So I'm going to convert unstressed volume too stressed volume. I'm gonna make it even bouncier. And so that's one way of getting my mean systemic feeling pressure up, and hence I increase the gradient, and hence I get more venous return and what's amazing, and you think about this. This is perfect. This makes perfect sense is that if you look at a vein and you look at an artery acceptable to adrenaline nor adrenaline, you'll see there are five times more receptors on the venous side than there are on the on the arterial side. And this makes perfect evolutionary sense because what killed are great, great great great great great ancestors was blood loss. So the very first thing I'd want to do if I was building a new human being, I would want to engineer it so that if I lose blood, a small dose of nor adrenaline, for example sympathetic nervous system, small dose the first thing it will do is squeeze the venous system, so it makes it more sensitive on the venous side. And if I'm desperately, really, really desperate, then I want to start squeezing the arterial side. So blood only goes to the brain, the heart and the loans. But the first thing I want to do is I want to just just squeeze the venous system. So basically make that air mattress a little bit smaller. So I convert unstressed volume to stress volume, and hence I raise my mean systemic feeling pressure and hence I get better venous return and float. But on the other hand, if you have somebody who's ill, for example this man who has been traumatized be very careful before you give any drug that will cause vino dilatations because that will make your ear mattress bigger. Convert stressed to unstressed volume and that will drop venous churn and drop cardiac output. BP. So we have to, you know, if you like to, uh, we often have to use curves, and I'm gonna try and stay away from curves, but I think these are necessary. So there's a you've heard of the starling curve. We talked about that. But there's another curve, and that curve is called the guiding curve. It's the venous return curve that a lot of people really aren't familiar with. And so if you look at this curve, you have instead of cardiac output on the Y axis, you have venous return, and on the X axis you have right atrial or C D. P. And we said venous return is the gradient. The difference between mean systemic feeling pressure, which is the pressure that's distending your venue ALS and your capillaries. That's very difficult to make you, by the way, and the C D. P, which was easy to measure but which is, um, the downstream picture. So it's only half of the equation, and there's the curve we have so there were starting off. So say you're CDP is low, so it's about let's say 00 to 1 or two, which is normally what RCDP is. If you were to raise the c d. P. We're going to get a lesser gradient. We're reducing the gradient. So the CBP is going up with the mean systemic feeling. Pressure is staying the same and then it goes down further. So we're getting less and less venous return until we get to the point where the CBP equals zero, uh, venous return. In other words, there's no flow. Okay, so that that that dot is that a CDP in this example of eight and at eight there is no flow know venous return see on the Y axis at zero. So that means if there's no flow, that means all pressures have to be equal. And so the C D. E. P. At eight will have to equal the mean systemic feeling pressure because you have no flow. And that's one way experimentally to measure mean systemic feeling pressure. We don't do that routinely, but in experimental models they can do it that way, so no flow equals. All pressures are equal a c e p that generates That's raised to the point where there's no venous return will be the point where equals mean systemic feeling pressure. Okay, Now let's look at the venous return curve again. So we now know that the mean systemic feeling pressure experimentally at least is equal to the point where the CBP generates zero venous return zero flow because they have to be equal. So what you can do is you can alter, just like the starling curve can be altered with inotropes, you can alter the venous return curve. How would you do that? Well, you can, either. Venoconstriction member, I just told you, you make the air mattress magically smaller. You give a small dose of vino constrictor like like low dose, low dose nor adrenaline emphasize low dose or so you make the air mattress smaller. So you converted unstressed distressed volume or you keep the air mattress the same size and you give volume. Give me a pump it full more full of air and make it bounce here. And both of those those, uh, those maneuvers will shift your venous return curve to the right. And so now what happens is the point where CBP and mean sneak filling pressure are equal. Hence know venous return. Uh, no flow. Now you can see the mean systemic feeling. Pressure has increased. You've just increased your mean systemic feeling. Pressure about either vino constricting, making your air mattress smaller, making a bouncier, converting unstressed a stress volume or filling it the same size air mattress. You feel even more air and you make it really bouncy. And both of those will increase your mean sustaining feeling pressure the pressure within that air mattress Hence you're going to get for the same CVP. You're going to get more flow, more venous return. Okay, so you just made your gradient bigger, and hence you get more flow. Now we've talked about the starling curve. We've talked about guidance curve, and we have to understand a couple of concepts. One is these two curves are going to use the same axes. You're gonna use cardiac output on the Y axis for Starling, you're gonna use venous return on the Y axis for guidance. As you just saw, cardiac output has to equal venous return. Cardiac output is the flow of blood from the arterial side of the left ventricle. Venous return Return is the flow of blood into the inferior and superior vena cava into the right heart. They have to be equal, and there comes a point. There's one point where the CBP is going to create the same cardiac output by stretching the heart member the transmural pressure. Remember the bag of Levis and Venous Return? So let's look at the two how they meet up so they're both on the X axis. You have the C D. P. Feeling pressure of the heart and the Y axis. You have cardiac output and venous return. They're both this. They have to be equal. They're the same. They're both flow different points in the circuit. So there's your venous return curve with your mean systemic feeling pressure. When the CDP generates zero flow so they're equal and there's your cardiac function. Curve your starling curve. And don't forget the CBP stretches the heart. That's what creates the, uh, cardiac work and the cardiac output. So there's a point where they're an equilibrium and there's only one point and it's there. Okay, so how does this work when you put the two together so Let's say you take somebody who is, um, on the steep part of their starling curve. Remember, we talked about the starting curve right in the beginning. Are you on the steep? In other words, are you fluid? Responsive? So the words you will increase your cardiac output by getting fluid, or you're on the flat part of your starting curve, in which case you're not gonna respond to fluid by increasing your cardiac output. So let's say you have somebody who's on the steep part of their starting curve. That's what we're trying to determine. Are you on the steep or flat part of your starting curve? So let's say you're in the steep part of your starting curve. You will respond to fluid. This is the exact opposite of that first lady we saw who was given 10 liters of fluid and didn't respond. She died. What happens here? So if I give you fluid, or if I vino constrict you with a small dose of know adrenaline, what's going to happen? You're going to shift your venous return curve to the right, and so your heart is going to get more blood toning back to it and because you're on the steep part of your starling curve. Your heart's got the reserve necessary to pump out that extra blood it's getting. So it's got some energy left over to pump out that extra blood it's getting from venous return. And what you see here is the CBP goes up a little bit, but the mean sustaining feeling pressure goes up a lot more. And so your volume of your heart is responsive to the increase in venous return, which is due to the main steam systemic feeling pressure increase, which is increasing more than your CBP. So don't forget we're talking about a gradient so your CD people go up a little bit. But you're mean systemic feeling. Pressure will go up even more, and hence you have a bigger gradient, and hence you have more blood coming back to the heart. And because your heart's got a reserve of energy, you can pump it out. Now what happens if you're on the flat part of your starting curve? Let's say your some old lady who's in heart failure and you think, Oh, the BP is a bit low. Do I give them some fluid? Well, if you do that and they're on their flat part of the starting curve. And this is exactly what we assume happened to that lady in the first case who died because she was given 10 liters of fluid and was not responding. What probably happened? She probably looked like this. So what would happen if you give her volume or vino constrictor? But in this case, they gave her 10 liters of volume. You're going to shift your C V P, and you're going to shift your mean systemic feeling pressure, but they're both equally increasing, so there's no increase in gradient, and then there's hence there's no increase in venous return. Hence, there's no increase in cardiac output because the heart hasn't got that extra reserve of energy to pump out that extra blood is gay. So the to go up, they go up together. But they go up equally and there's no increase in the gradient. So that's where the first lady who died was. She was not on the steep part of her starling character. He was on the flat part. What about the flip side of this? What happens if you suddenly make that air mattress bigger. You convert stress to unstressed volume. You lose the bounciness If you have somebody like the gentleman who had a fractured femur and a traumatic, um, say a ruptured spleen and we gave him some morphine because he was in pain. What happens in his case, you're going to convert that air mattress is gonna get suddenly bigger. You're going to lose the bounciness because you're gonna, um, reduce your mean systemic feeling pressure. You're going to convert stress to unstressed volume. You're going to get the curve shifting this time to the left. So it's vino dilatation, or you lose blood volume or both. And now, because you're on the steep part of your starling curve, you're gonna drop your main stemi killing pressure and you're gonna drop your cardiac output. So it's going to look like this. You're gonna reduce your gradient, hence reduce your flow towards venous return and hence reduce your cardiac output. So let's look at a couple of quickly couple of clinical examples. So what do these cases have in common? Sorry. BP to interrupt. Dr. Vogel, we've got 10 minutes left. Yeah, and we need to do questions and feedback Well, I'm almost done. I always have an hour. So this is my 12th lecture, if you don't mind. Okay, so what happens if you, um these cases BP crash after rapid sequence induction and improve saturation with people? Would you basically pumping the lungs full of air to or full of gas to try to open up? The alveolar like to get more Oxford. OK, clinical case. Someone has a small bowel obstruction. The Unisys wants to They look to get dehydrated. Unisys wants to take them for a laparotomy in the operating room. They do what they call a rapid sequence induction. In other words, they want to put them. They want to anesthetized them and paralyze them to rapidly put an endotracheal tube in them so they don't aspirate gastric juice into their lungs. It's a common procedure done by Unisys. It's a and they're obsessed by not crashing BP by doing this because it does drop BP. They use propofol, which is the anesthetic agent, and rocuronium, which is the paralyzing agents. Muscle relaxing, BP crashes. Why, Okay, So what happens here is you vino dilate with your anesthetic agent. So you convert stress to in stressful. And you made your air mattress bigger. You cause a drop in me Systemic feeling pressure. Now everybody who does anesthetics knows this, But they all forget is that once you paralyze the patron, you also have to ventilate them. And they all forget this. And when you ventilate somebody, as we said with a syringe and squeezing a fluid filled container, you're gonna raise your CBP. So there are two causes of a drop in blood pressure and almost all the nieces forget this. Um, I'll go quickly with this one. This is just, um if you have someone with severe pneumonia, you might want to increase the pressure in the on the ventilator to pop open their Alvey coli. And you're thinking great is this is a success. Well, it's not because you increase their oxygenation, so you'll see on the saturation on the on the screen. Your saturation improves. But if you're not measuring cardiac output, you may see that it drops. And so overall, what your overall goal is is oxygen delivery, and that might go down. Not always, but it might do so. Don't don't get trapped into looking at the wrong parameter. Okay, In this case, it's because you're squeezing the heart and you're raising this CBP and you're reducing the gradient, and hence you're going to reduce your venous return. Okay, I'm gonna have to go quickly. Here. I'm afraid so. This is somebody who has got a very septic abdomen. They received three liters of the true story again. BP is low heart rates, fast spiritual rates, fast urine outputs past. So what we're going to do? Basically said we're going to increase that person by first optimizing filling right? And then if that doesn't work, we use inotropes that we just said, Well, I hate to come back on myself, but maybe not because there's more and more evidence now that by giving fluid a lot of fluid, we can make you worse. And so the non survivors have a lot more fluid on board than the survivors who are very They're new patients. And cumulative fluid balance is an independent factor for mortality. So some people today, based on the knowledge and based on the principles I just explained to you, they're saying boo, They're saying that Oh, sorry. There's a mistake here. That's okay, They're They're saying that maybe we ought to be using, uh, a little bit of a little bit of vino. Um, Aveno constrictor. No words nor adrenaline because it spares a lot of fluid. So basically, we're doing is we're reducing the size of the air mattress and we're filling. You got to do both. You can't just use your adrenaline that will kill you, But maybe we have to do a combination of both. So maybe we need a new paradigm. So maybe it's not just filling. Maybe you want to do a very small dose of your adrenaline or vino constrictor to make the air mattress a little bit smaller so we can get away with a little bit less fluid. This is just This is the same slide again. I just mistakenly left it in bear with me. So basically, you might want a combination of a little bit more adrenaline, but with with fluid as well. Not one without the other. And this is becoming more and more mainstream talking about converting unstressed stress volume and not using excess fluid because it worsen outcomes. And here's here's one thing I think it's important to know If you look at a CLS, they say you want to treat hypovolemia with rapid infusion of fluid, and we know that if you have a traumatic cardiac arrest you to hypovolemia, it's almost always fatal. Why is this? So why do they tell us? Use fluid when we're gonna use fluid and we'll kill our patient's who have traumatic cardiac arrest and the The reason is very simple. A TLS the trauma system guidelines say severe fluid loss 40% or more that will, cause, you know, very severe hypoglycemia. You lose about two over over two liters of your five liters of blood volume. And if you were to infuse through a large cannula and use gravity, you can only infuse about 100 mils a minute. So that means that for 20 minutes you're going to have somebody who's heart is going to be essentially empty. So that's way too long. So that's why you quickly want to get in a small dose of your adrenaline and fluid. Okay, because you want to make that air mattress smaller and and convert unstressed a stress volume. But you can't just rely on fluid. It just takes way, too long and you will get a person who's dead at the end. And this stuff is now mainstream. And these are just articles from recent articles in the last year or two, and they're talking about unstressed volumes. Uh, mean systemic feeling. Pressure. All these things I'm talking about are very mainstream now. Okay, so I'm just finishing here. So we just showed that the C d. P. Has two functions. On one hand, it opposes venous return. It stretches the heart. It should cause of your transmural pressure along with your inter thoracic pressure. So it But it opposes venous return, but also drives the ventricle. Okay. And the end of the day, what really interested in is oxygen delivery? And we said earlier on the cardiac output You said this in the first lecture. Maybe the most important factor determining cardiac output and oxygen delivery and oxen. Cardiac filling is probably the most common thing you're going to be doing. So you have to really understand these basic principles because it's it's if you don't, you're just basically doing the same thing over and over again. But you're guess so. That's it. Any questions, please? But any questions no questions. Okay, Wonderful. Okay. Well, um, thank you very much, Doctor Vogel, for a really interesting lecture. Um, since we've got a few minutes left, could everyone please do the feedback? It's really important for us. Um, and then right at the end, Um, I'll post the certificate for this lecture in the chat. Uh, yeah. Oh, sorry. Doctor Vogel. Someone's asking a question. Very good. Um, they're asking if you could quickly recap M S f p and any dangers to having having it more positive over CVP. Uh, first of all, no dangers if you don't have it higher. If it's not higher than CBP, then you're dead. Okay? Just remember to get flow. This is not medicine. This is physics. To get flow, you have to have a pressure. Gradient. A lake on a mountain that's flowing into a river will flow to the sea. So the high the high pressure from the high level of the mountain lake will flow to the low level of the C. The greater the difference, the more flow you get. If you have them equal, there's no flow. So if that means systemic feeling, pressure was to be equal to the CBP, you'd have no flow. And what I was saying to you was that if you were to look at someone who had, uh, we could measure their radio artery pressure and we measured their CDP. And then they die. Their heart stops, the pressures will all be equal. There's no flow. You're dead. But the pressures in those systems will not be zero. They'll be reflecting the stretching of the blood vessels that mainly the venue ALS and the the the veins. And that's the upstream pressure that drives blood blood back to your heart. So you want a mean, systemic feeling pressure that's higher than the C D. P. So either you raise the mean steaming feeling pressure or you lower the CBP. But you don't want them to be too close to equal because you'll have no floor, have less flow and flow we're talking about is blood coming back to your heart, which eventually becomes cardiac output. The blood blood circulates. Okay, Thank you very much, Doctor. Um, I think we'll end now in a minute. I'll just post the certificate in the chat and you have to download it. And if there's any issues with downloading the certificate. I'll put an email in, um so you can send. You can send a request to this email together. It's difficult if you aren't able to download it here. Yes, second.