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Hello? Hello? Hello there. Hello. Hi. Doctor Google. My name is Anna. I'm one of the moderators. Okay. How are you? Uh, where are you? Okay. Hello. Hi. Can you hear me? I can hear you. Great. I think I think one of the other moderators was supposed to be here as well. So Okay, I just want to make sure last time we had a few glitches and I guess, given what's the circumstances will be more on your end of mind. So it doesn't matter, really. This is going to be recorded anyway, Which might be quite a wise thing. Yes, definitely. Makes sense. Um, yeah, but I'm here. I'm happy to moderate so I can send some housekeeping and things down the chat. Okay. Well, I have an hour, so let me know when I can start. If I If I can start, Uh, yeah, I think that's good. Just if you give me two minutes. Um, Thank you. Okay, so hi. Good afternoon, everyone. My name is and I'm one of the moderators. Welcome to the time to Crisis Rescue Foundation. Uh, Ukraine Medical School, UK Elective program. Um, so please remember these lectures are for displaced medical students. The lecture will be recorded. It will be about 40 minutes long with 15 minutes, uh, For questions and comments, you'll all be muted. Questions and comments will be placed in the chat, and, um, we will moderate them as the moderators. Um, and please remember to complete the feedback as well. Um, and welcome, Doctor Vogel. I believe you'll be delivering a talk on anesthetics. Uh, well, actually, it's more to do with the intensive care of physiology. Acute medicine. It's the clinical application of physiological principles. Amazing. Thank you so much. And I'll give you the floor, then. Okay. Well, get my screen up here. Host disabled participant Screen training. Uh, so you have to let me hear my screen, please. Sorry I'm not the host at the moment, so let me just it's saying that the CRF is the host, okay? Yeah, This happened last time as well, so I can't hear my screen until someone allows me to. Um, yeah. Sorry about that. I'm trying to see if I can. Okay. Did that work for you? Now, if you check. Yeah, that's it. Okay. Thank you. Sorry about that. Uh, where am I? uh, Can you see that? Yes, we can see that. Okay. Uh, video panel. Okay. I just want to hide the panel. Um, yeah, that's it. Okay. So today, um, we're we gave a talk or I gave a talk. Last greetings, everybody. I'm Dr John Vogel, and I'm recently retired consultant in intensive care, medicine and anesthetics. And the series of talks I'm giving will be about the clinical application of physiological principles. This is important because quite often, we learn these principles in medical school, and we sort of think of them as boring. We have to get through them to be able to do the cool stuff, which is treating our patients. And what always strikes me is how applicable these principles are and how you ought to be able to use them and should use them in in your future clinical work. So last week, we talked about the overall, um uh, structure of format of using oxygen delivery as you're sort of major model for how you deal with the patient. Overall. And we said that the most important, um, the most important of the three factors those were cardiac output. Hemoglobin saturation was cardiac. output. Um, and probably the most common thing you will do to influence cardiac output throughout your career is giving fluids. So the next three letters are going to be on fluids. And today's lecture will be on the consequences of Ms guessing your fluids. So you give too many or too much or too little, and the consequences may surprise you. Okay, so we're going to start with a true story, a dramatic clinical case that that I lived through a few years ago and this, uh, this I will never forget. So, um, this was a 15 9 year old gentleman who's having a minor procedure. He's having his hemorrhoids operated on. And he was a fit building, a builder, very healthy. And during the during the procedure, he suddenly had an anaphylactic reaction to one of the drugs that was given, and he developed a massive myocardial infarction. So he had a massive heart attack. He was taken to the intensive care unit in cardiogenic shock and knowing that cardiogenic shock has a mortality of about 50%. Um, this was a serious, serious case Now. When he arrived in our unit, he was intubated. He was being ventilated. His BP was very low. His cardiac output was very low. Um, he had modeled skin. All these are signs of the very poor profusion. His saturations of his oxygen saturations on the pulse oximeter were were very low. And he had masses of pulmonary edema, sort of pink fluid coming out of his endotracheal tube. Now, the, um this was a desperate situation. He was on. Also, he was on maximum doses of heart stimulants inotropes. So the question now is this Do we give him fluids or not to try and improve his cardiac output? Now, trying to create a construct of what we imagine happening, this is a normal starting curve. So on the x axis, you have the feeling of the ventricle, and that's often what you measure is the right atrial pressure with a CBP and on the Y axis, you have the cardiac output, and normally this is what a curve are. Curves your curve and my curve would look like we're on the steep part of that curve. And which means that if I fill you, you're going to normally increase your cardiac output, uh, dramatically and get a little bit of an increase in feeling pressure as well as filling. But what do we expect with this person? Cardiogenic shock we expected, given his heart has been so badly damaged from the in fortune that his curve would be very low and very flat and very much to the right. That means that for a lot more pressure in his ventricle, he's gonna have a very low cardiac output. And if we try and fill them, what we imagined happening would be this He would get almost know, improve improvement in cardiac output. However, he would increase increase massively, his feeling pressure, and by increasing his feeling pressure he was he would make his pulmonary edema worse. This is what a normal this is just what they call sidestream dark field Spectracef. It's a video of the mucosal filling with the micro circulation. This is what a normal micro circulation looks like. You can see they're nice. Big boulevard and small side streets and rolling cells, white cells and red cells. That's normal. This is what cardiogenic shock looks like. And when you look at this man overall, you can well imagine that's what he would look like. So what was what was the drama in the situation? What was the dilemma? The dilemma was the following the dilemma was he was on absolutely every support we could give him. But his cardiac output was very, very low. He would not survive the way he was at the moment. His only chance would be to transfer him to a coronary catheter lab so they can stick a catheter into his coronary artery and hopefully find blocked coronary artery and revascularized. Now, the problem with our lab for technical reasons was closed that day. So we had to transfer him to another hospital was only chance. Otherwise, he was definitely going to die with this, but he was too sick to transfer. That's what the ambulance service said to us. And they were right. He was the way he was. He would die in the ambulance they were going to take. So we have to do something to give him the slimmest chance. And that would be to get him well enough to get him into the ambulance and to a cath lab. And that was a small small, uh, possibility. But it was the only one he had so we can't improve his cardiac output. Somehow we have a massive doses of drugs. He's going to die. What about fluids? Now, the problem with fluids, as we just saw with that construct I just showed you was that if we're wrong and we, uh, increase his filling pressures, we're going to make his We're going to make his pulmonary edema worse. And that will reduce his saturations, which will reduce his oxygen delivery, which we talked about last week, and that will That will mean he's dead. So basically, if we gave him fluid, we can kill them if we don't give him fluids going to die. I mean, we're in a really difficult spot. So what would you do? Anybody? Well, I have to be quick about this. What we did and this Absolutely amazed because I wasn't expecting this. We wondered, how can we give him fluid without killing it if it if they didn't work? If it didn't work and what we did is we lifted his legs. We did what we call passive leg raising and to my other amazement, and I mean, I said I really was amazed his cardiac out his BP came up, his cardiac cath came up and we managed to transfer him to the tertiary center. They did an angiogram on him. They found she had a blocked left anterior descending coronary artery and they refused it and he got better. So that was where this idea of where where you get fluid or not is going to be dramatically important. So today we're going to talk about what happens. What are the consequences of getting too much fluid or two little flute? So let's start with too much fluid. Now. This is an interesting study that, um even though the circumstances are not necessarily what will be reproduced in your hospitals. This was something that just basically made people wonder to think this was done in Africa, in resource poor countries, where Children who were in septic shock and severely ill with various, uh, infectious diseases were given fluid boluses on arrival to the hospital. These were sick kids or they were not. They were given just maintenance. Fluids very slowly dripped in. And what they found was the mortality was higher and those kids given fluid than those that weren't. Now again, I would say the circumstances so different to anything you and I would come across. But it just made people wonder. Maybe fluids are automatically a great thing. Maybe there are downsides to fluids, and in fact, we know from multiple studies. And this is just one of many, many studies that if you look at the fluid balance in sick patients that are in the hospital when I see you for several days and you look at the two groups of those who survive and those who don't survive, the non survivors have an increase in their fluid balance. In other words, they have received more fluids than those that didn't. Now is that cause and effect? Or is that association? It could be a little bit of both. The sicker you are, the more fluid you need. Hence the unless you're likely to survive. But there's definitely a signal there that too much fluid is not good for you, and it's biologically plausible as well. So what is the first thing that too much fluid will do? Well, it may endanger or will endanger your glyco. Okay, Alex, Now you're probably saying the glyco what? Okay, so we're going to talk briefly about the glyco. Okay, Alex. And I think this is a very interesting and exciting, relatively new discovery. So if you go back to your medical, uh, your medical school days, which is now for you, Um, there's an Ernest Starling who gave us the starting curve to give us several things. But he gave us the single vascular barrier model of fluid maintenance of fluid dynamics. And I'm sure you remember this. This will look familiar. So in the intervascular space, you have pressure hydrostatic pressure. That's forcing fluids out into the interstitial space through the endothelium through the cliffs of the endothelial cells. But you also have proteins, 80% of which are albumen, which some fluid back in. So you get this sort of circular fluid movement, and the excess fluid that goes out is taken away in the lymphatics. So that's the kind of model we all learned I learned in medical school. What experimentally? Recently, they've noticed that if you make the colonos ammonic pressure inside and outside the blood vessel equal, these are experimental animal models. The food was still sucked in. Now this totally negates what happens with starting. It shouldn't happen. So what's going on? Well, this is the model that has been proposed. So there's your intervascular space, and that's abdomen is the little dots there you have your endothelial cells. There's the interstitial space, and the density of the dots is the same in this model. This is just to represent a cartoon representing what I'm talking about. When you have above the endothelial cells on the blood vessels side of the endothelial cells, you have what they call the glycolax. And there you have a dense accumulation of albumin molecules, proteins feel like. So what happens is that in this case, the concentration of the album in inside the blood vessel is not as important as the glycolax, which is has to be intact. And it will, um it will gather, concentrate your protein. So what happens now is that the gradient that sucks fluid back in is between the Inter station and the the Intact. Like Okay, Alex. And then, of course, as the blood sweeps away, um, it will take the fluid downstream. So the key here is not the albumin in your blood. It's the albumin in your intact. Like Okay, Alex glycolax is not intact. You're going to lose fluid, and that's what you see. And does this glycolax really exist? Well, if you look at it under an electron microscope, that's to micrometers, and this is at 0.2, and you can see these kind of hairy, hairy brush water. And the glycolax are just proteoglycan and glycoprotein. These are filaments, and they're very, very active biological there in all the blood vessels and lymphatics, and they've got an incredibly important role to play. And it's, um it's quite exciting when you see what it actually does. So what is the Glyco College student? This is a cartoon that explains. So you can see that you have the urethra sites. You have plasma protein in the in the blood. You have platelets, you have monocytes now the glycolax. And what's amazing is that they're like these filaments. If you think of it like a young sapling, a young tree and the flow of blood will bend the tree like the wind will blow, will bend a young, strapping young tree, and the the end of this glycolax filament is attached to a mechanical receptor, and that will determine how much nitric oxide is released. So the size of the blood vessel is controlled by the glucose being intact. You have an willebrand's factor, and you have various antithrombin you have. So basically it's like your body's Teflon. It stops platelets, red cells and monocytes white cells from sticking to the wall of the vessel. If it's intact and he's on two throbbing, as I say So it's like your body is Teflon and there's occasionally one of these little filaments gets snipped off and float downstream. And that's the plasma proteoglycan, which is a fragment of the glycolax. So what happens if it's damaged? Well, you get a lot of these filaments floating downstream. You lose your nitric oxide. Synthes. So what happens if you have someone in septic shock who has a totally destroyed like? Okay, Alex, one of the the the commonest signs of some one in septic shock. Because they have total vasovagal plegia vasodilatation they can't constricted vessels. Um, as I said just a second ago. The other thing is that you have mono monocytes sticking to the cells. You have platelets at a hearing, so you're gonna get clots and you're gonna get a leak of protein because I just said to you, it's the it's the entire electrical. It's when it's high concentration of albumin that's going to maintain fluid being brought back into the blood vessels. And interestingly enough, as I said a second ago, the filaments have got a very strong anti coagulant effects. So it's a bit like Teflon, and one of the filament is called heparin sulfate. And this heparin sulfate, if it's snipped off and float downstream, will cause what we call auto heparinization. And I'll show you a second. What, that what happens when you when that happens? So what? What triggers damage to look like your cakes? Tumor necrosis factor. You get the sepsis, so it's a cytokine, endotoxin gram negative infections, leukocytes ischemic re perfusion injury and atrial natriuretic peptide ANP. We'll come back to that and you'll see this coming back in this in this talk later on, and then you're going to get capillary leak, which is the point of this talk is about maintaining fluids and how much fluid you give or don't give. So does this matter well, if you look at someone is high in your urine, which is one of the family of filaments in the glands. Okay, Alex, there are others as well, but this is just as a as a marker, and you look at someone who's healthy. There'll be a few in the bloodstream because they do get ripped off and float downstream in the blood. If you're septic, there's more. If you're severely septic, there's even more. And if you're in septic shock, it's off the scales. So basically, I think you're going to collect. And you know, measuring in the plasma is a sign of very important sign of severity of illness. And it's a prognostic fact. So what about ANP? We said that was, um, this peptide that's released when the the Atria are stretched by overfilling. Usually the estrogenic volume, excess volume loading. Uh, it's released into the blood stream. So does this happen well, if you look at this study during operations, look at different time periods. If you take one group and give them a minimal amount of fluid, you'll see the AMP level is relatively low. If you give more fluid, high fluid intake, you have a higher MP. This is completely understandable, and it's biologically totally plausible. So what does a M. P do does it really damage look like dulcolax? Well, in this animal study, this was a control model. This was the image, uh, micro electron micrograph of a like a collection of blood vessels. It's glycolax in in dark in the dark haired area there, and if you give a recumbent a M. P, look what happens, it completely destroys the glycolax so overfilling somebody will damage the glycolax through the release of a M P. And so the glycolax, which I've just described from the point of view of of filling is very important, has a lot of a lot of really vital functions. It's a vascular barrier function just mentioned. It's your body's Teflon stops thrombocytes leukocytes from sticking. It controls inflammation, controls, vessel dilator diameter. If you lose your nitric oxide production, then you're going to have a blood vessel that doesn't respond by constricting or dilating. And if you think this is not important, well, this is These are just some of the studies I just picked off off the top of my head recently. It's been involved in sepsis, preeclampsia, renal injury, D I C. Micro circulation, disease, Alzheimer's coronary syndrome trauma, cute lung injury, Deng you name it Glycolax Glycolax is really the flavor of the month at the moment, so you know, it's important to know about this. And just as I said to you earlier, if you damage your bladder, Calix, you lose that Teflon and you get what they call auto heparinization And what, like what d. I c disseminated intravascular coagulation is. You get clotting and you get bleeding, clotting and bleeding, and that's what it looks like. There are clots, and if you look down the stream there probably bleeding, it's horrendous. The other negative aspect of getting too much fluid is back pressure. You get the damning back and you get venous congestion of the various organs. So let's look at this. Let's look at a couple of the organs that are damaged by overfilling. One is your kidney. Now there's something called the Cardiorenal syndrome, and one of the signs of, uh, there are different types of type two. The commonest kind is when you're in end stage. Heart failure often what? One of the last things that happens is your kidneys fail and everyone thought for years. It's because you're not perfusing your kidneys, not forward, refusing your kidneys, so there is no blood going to the kidneys, not enough. In fact, that's not true. If you look at the glomerular filtration rate on the Y, Axis is a sort of a surrogate of, of, of filling or flow to the kidneys, and you look at different groups. That's a person who has a high cardiac index. It's a high cardiac output, same thing and a low c D E p too low filling pressure. There is your g f r. So that someone who's healthy you have someone has a low cardiac index but a low C D E p. They have very similar in PFR. So it's not the cardiac index that's important. It's the C D. E. P. In this example so far. But if you have a high cardiac index and a high CCP to a high feeling pressure, um, so the venous return can't take place. And if you have a low cardiac index and a high CCP, so the commonality here to to cause a low familiar filtration rate, strong words, kidney failure or the high CCP. So if you have too much fluid and the heart is over distended and you raise the pressure, the high CCP you will cause back pressure Venous engorgement of your kidney and your kidneys, um, is, uh, is encoded by a capsule. And, uh, the road is fashion and they can't extend, so it basically can't. You can't get the blood out, so it's venous congestion rather than cardiac index. It's the most important hemodynamic factor worsening renal function in advanced heart failure. So the problem is to fix that you want a new heart, not a new kid. What about the liver? Well, there's something called cardiac liver or nutmeg liver, and I've seen this throughout my career quite a few times. People are in stage. Heart failure can come in with cirrhosis, so it's not because they drink. It's because they have this excessive venous congestion, which damages the liver. And maybe I won't say it's most important. But one of the things that I see quite often I saw quite often in intensive care with somebody who has heart failure Again, again, these are all reasons to have a high central venous pressure, and this back pressure will cause a raise, atrial pressure or high CCP and venous congestion. And this time the congested organ will be the contestants. So what happens is the contestants will now become leaky. And bacteria in your body has got about 100 times more bacteria than it does cells. And most of them are in your intestines. And so this incredibly bacterial rich environment will translocated into your lymphatics and your blood stream and will cause release of proinflammatory cytokines and cause cachexia, anorexia and all the problems that go with the Proinflammatory state. So right, ventricular failure and intestinal congestion can trigger translocation of bacteria. And I often have a battle, not a battle, but an intellectual discussion with the cardiologist who wanted us to take somebody who was sick with sepsis. And I would tell them I said, Listen, if we can fix the sepsis temporarily, But the problem is the heart and this is for the reason we said that. So what about not enough fluids that was too much, too much fluid. You're gonna potentially damage the glycolax that all important glycolax, which is so vital to your health. And secondly, you have all this, um, localized venous congestion. Uh, that can damage organs as well. So those are two reasons to not give too much fluid. What about not enough fluid? So this is what happens to when you don't give enough fluid. And this is a really fascinating study that was done many years ago, and I knew the authors of this, and what they did was they took volunteers, healthy volunteers, doctors, in fact, and they took blood off of them, and they took it into into into a look what's they took 1st 600 mils of blood. And then they did some measurements and they took a 2nd 600 miles of blood. So that's 1.2 liters. That's quite amount of blood. And they measured things like heart rate, BP. And they did a measurement of cardiac output. Noninvasively using a super external Doppler doesn't matter, but they used a measurement of cardiac output, uh, non invasively, and then they use something that I won't be able to go into detail with, but just, um, it's a measurement of this flow of blood to the stomach. And there are several ways of doing this, and the idea is that your four gut flow to your stomach may be the earliest organ that will suffer if you lose blood, and that's what they're going to look at. So what did they find? The 1st 600 mils? That's pretty much what you give when you give blood. They found that the BP, heart rate and cardiac output were up, down. Same the same. So think about this. You could lose 600 miles of blood, and your nurse in the work will say BP is fine. Heart rate's fine. Don't measure the cardiac output, so everybody's happy. What about the measurement of flow to the stomach? And they used something called Gut intramucosal. PH. It doesn't matter. The technique doesn't matter, but it was flow to the stomach. So the lower the pH, the less the flow to the stomach, it dropped. So in this situation, can you have someone who's lost 600 miles of blood? And all the things that the nurses will measure in the ward are fine. But if they were to somehow measure with the flow to the stomach and the four go, they'd see it's not funny. So what about the 2nd 600 mils? That's 1.2 liters now. Now, BP and heart rate again. Those are the common things that nurses measure no change. So that's a lot of blood loss. And there's still no change in blood pressure and heart rate cardiac output. It's going down a little bit, but we don't normally measure cardiac output awards. What about your Your gut flow has measured by the interim mucosal pH dramatic drop. Now, what was really fascinating about this was that the volunteers I went out for a drink with the guy who's the main author of this, and he told me something that really blew me away. And that was all the volunteers had the blood given back to them immediately so they'll be fine, right? Well, all of them after re transfusion, recovered, but they all had flu like symptoms for about 48 72 hours, so they had, like a mild flu. Mild flu probably is the release of side icons, so they were probably suffering from translocation of bacteria. Now that's me guessing, right? That's what we're all guessing that but doesn't make. Is it biologically plausible? Absolutely. So this is one study where they looked at again. It's a different way of measuring flow to the stomach. You're using something called the CO2 Gap Doesn't matter. But just basically saying flow to the stomach. And they looked at tumor necrosis factor, one of the important cytokine, one of the pro inflammatory proinflammatory cytokines and as the CO2 gap. So as the flow to the stomach went down, the gap got bigger. The tumor necrosis factor went up. So that kind of reinforces this idea that there was a strong correlation between the flow to the stomach and cytokine release. Hence the flu like symptoms. Now what about I mean, we can take this one step further if you and this was a study done in healthy people who were being exercised to the point where they assumed that the splinting vessels, the vessels to the gut. We're, um we're under perfused. So what they did was they used again a thing called the CO2 gap. Um, again, it doesn't. The technique doesn't matter, but as they push themselves cycling hard, 70% of the maximum wattage, so they're circling is 70% of the maximum. And as you can see, that gap is getting bigger. And the reason that gap is getting bigger is probably because the blood is being diverted to the muscles and not to the gut. And then when they stop cycling, everything came back to normal again. But they then measured something called a fat, intestinal fatty, acid binding protein. It's like your guts troponin, and it's a marker of how leaky your intestines are. And guess what when they cycle to 70% of the max, the if it went up. In other words, the guts were getting leaky. Leaky means release of transmitting the transportation of bacteria, and it probably means release of side cuts. And when they stop, they came down again. So I thought it was fairly interesting. So here here was a dilemma that was brought to the attention of surgeons many, many years ago. It's been a dilemma that's been around for decades now, and that is after surgery. There's often poor production of urine, so patients are often all a jerk after surgery, and the question that's always been asked for decades and decades now is will extra fluid be required to, um, is the is the sorry is the reduction of urine, a sign that the patient is under filled. Or is there another cause of the reduction in, um, in urine output and oliguria? And by giving fluid or not? Well, we reduce or increase the postoperative complications? And this has been a major, uh, point of discussion and debate and even acrimonious debate for many, many decades. So I don't want to go through too much history, although it is absolutely fascinating. Um, there was the first model that was proposed by an American famous American surgeon, and he basically this is before 1965. You're not. But this debate is still going on. And he said, The reason that you don't produce your is not because you're dehydrated because your body is reacting to the trauma, the stress of trauma so your body surgery is nothing but controlled trauma. It's like being hit by a car, so your body's natural hormonal or neurohormonal reaction to the stress of trauma is basically to retrain to retain fluid, and therefore you don't pee Paula uric. So he felt that don't be tempted to give fluid because you're going to overload these patients who don't need it, and if you get fluid, you have fewer If you don't have sorry, If you have a little fluid, you have less complications. And if you have a lot of fluid, so he's saying, basically keep them relatively dry. And in 2018, there were two studies that seemed to confirm this idea, and one said Oliguria was from nonrenal stimuli, including the pain, nausea and the trauma of surgery. And the second study said that they said the same thing, and they said, basically, oliguria the lack of production of urine after surgery could be anticipated and permitted. It's almost like a normal reaction. Okay, that was one school thought, But there's another school Now again, this is a long story that I won't have time to go into. But it is absolutely fascinating, and I know if you've heard of something called the Third Space. The third space was a a theory that was proposed by a man named shares a surgeon again. And what he said essentially, is that when you traumatized tissue, it swells. So if I take a hammer and smashed my elbow and break some of the bones, my elbow will swell. Now the fluid in my body that is going to fill that edema to space is no longer available for circulation. It's basically sequestered, and that's what he called the third space. So the more the trauma, the more the fluid that you have is not is not available for circulation. So when someone is traumatized, he felt you have to not only, for example, if you lose a liter of blood. He didn't say You have to give a liter of blood. That's fine, he said. You have to give a liter of blood and lots of fluid to fill that, or to compensate for that loss into the third space. And his model was this the opposite to the previous one? If you want. If you want a few complications, then you want to have a lot of fluid. And this had a major major impact on the surgical services in the military and the United States. For decades, I worked in a in the second biggest second largest trauma center in the United States, maybe the world, and I saw firsthand how this works and it was exactly what I just said if I if I had someone who came in and they lost leader of blood. You get a liter of blood and you get 678 liters of crystalloid. Not, you know, a cellular, uh, electrolyte fluid. And I mean, they just poured it in port again. Did this have consequences? Oh, yeah. But before I go on, this is just to remind me to remind you that the gentleman who proposed the third space was the doctor who received President Kennedy when he was shot in Dallas. So did this have consequences? Yeah. This had major consequences. This is what a normal lung looks at, like at autopsy. Okay, so this is a normal lung. You could take someone who's died and they had an autopsy. That's what your lungs look like. It's like it's about 708 100 g. It's like a sponge. During the Vietnam War, when this theory was being adapted, uh, they came across something called Shock Lung. What was shock Long. They found that after successful resuscitation from circulatory collapse, so the so the blood volume side of things was being successfully resuscitated. What happened next was they were getting pulmonary edema from the from the liquid. So basically they were successful on the blood loss side of things, but they were getting pulmonary edema and the lung they they looked at now look like this shock lung. So you go from a normal lung. Looks like a sponge to a piece of what looks like a piece of liver. And this was the beginning of the recognition that too much food wasn't good. But that was the debate between the two, uh, do groups. And in 2018, yet again, another study looked at restrictive fluid as opposed to too much fluid. And they found, if you didn't give enough fluid, you had a higher rate of acute kidney injury. So here you go. You have one group saying, Keep it, keep them dry. Then another group says no, Fill them up and they go back again. Keep them dry, fill them up. So you probably want to be somewhere in the middle. We call the sweet spot. Oops. Okay. So are you confused? You want to be because I think a lot of people are. And I have to say to you that one of the things as a young medical students, I would have to, um if I can give you a bit of elderly advice is you have to feel comfortable with uncertainty in medicine because they're within bounds of reasons. But often we are. Things are not quite black and white and cut dry. You have to be comfortable with uncertainty, and you learn how to live with it. In this case, that's what we're dealing with. So there's one model that I thought was kind of kind of interesting. And there's some people were pushing this and they were saying Okay, well, if we're not sure whether to give too much or too little what if we were to before an operation? Let's use the starting curve that we talked about in the beginning. There's your X axis is your feeling of your heart and there's your Y axis is your cardiac output. So let's measure it before we start, and let's fill you until we get to the point where we call. That's someone who's fluid responsive. Okay, so that means I'm a steep part of the starting curve. If I give you fluid, you will increase your cardiac output, your fluid responsive, and you won't get a lot of feeling. Pressure. Okay, Lots of cardiac output. Little little bit of increasing pressure? Not much. But if you're if you get to the point where you're beginning to enter the flats part of the curve now, if you keep feeling you're going to get a little bit of cardiac output increase not much, but a large, increasing pressure. And that's bad for you. And that's what we call someone who's fluid unresponsive. So you're no longer flu responsive. So the some people thought the goal should be some some people call this goal directed therapy is to take someone who's on that steep part and push him right to the point where he's just starting to become fluid, non responsive and that would presumably optimize your your cardiac output. You call it optimization. Well, that's interesting, but let's go back to our goal like a callous again. You'll see what I'm talking about. This There was a team that wanted to examine this, and they wanted to see if this actually worked. And so what they did was they took animals, pigs, and they gave them severe pancreatitis, which is a very strong inflammatory, um, disease. So it's a very strong inflammatory signal, and they took one group, and they just treated them. They measured the cardiac output is before they gave them pancreatitis. So this is These are normal, healthy pigs. One group and they measured all the cardiac outfits before they got pancreatitis. They then took one group, and they gave enough fluid just to get back to what was the normal value Before they got pancreatitis and the second group, they gave enough fluid to get them to the top of that starting curve. So we just talked about a second ago, getting them optimized so they were no longer fluid, responsive. And what did they find? It's a normal stroke Volume. Stroke volume is cardiac output per beat. Okay, so it's because it's cardiac output. So heparin sulfate is one of the family of filaments that make up the glycolax. And I told you a second ago it's kind of like your body's Teflon. And if you if you oughta heparinize you nip off the heparin sulfate. It flows downstream, so the denuded blood vessel wall will now allow clotting and heparin sulfate that's floating downstream. Well, heparinize you. So hence D. I see. So what did it look like? And that's kind of the thing you'd measure you could measure if someone was being is inflamed. So in the normal stroke volume, there was a little bit of hyper and sulfate in the maximize stroke volume. There was a lot. So you're maximized. Stroke volume seems to indicate that something is damaged from You're like, Okay, Alex, if you measure I l six, which is one of the proinflammatory cytokines. Now, don't forget these. Both groups of pigs had pancreatitis. So strong Inflammatory disease? Yes, there was ill six from the inflammation of the pancreas in the normal stroke volume. So these are pig's that have the same cardiac output that they started with and the ones that we're maximized. We're trying to optimize their cardiac output much higher. And what they found when they looked at the pancreas under the microscope was they found that by maximizing your stroke volume, you cause more severe like Okay, Alex degradation. Hence the heparin sulfates a lot higher and under the microscope, they found that pancreatic inflammatory demon was a lot worse compared to just normalizing the stroke volume. So filling in this example may not be the ideal thing. It was probably due to the release of H and P. Remember, we said a M p actually electronic peptide damages of, like, narcolepsy. You over fill these these animals and you stretch the heart. You get a M p release. You damage the glycolax, which causes leakiness edema, etcetera. So, to recap, you can either under or over resuscitate patients. And if you do, you're going to, uh, increase the mortality. So if you under fill, you're going to get, uh, scheme of the organs like the gut. And we saw that earlier with, uh, under filling of the stomach or the intestines with the, uh, the fab, the intestinal fatty acid binding protein and leaky, uh, intestines. You're gonna get transportation, you give too much, you're going to have the problems of back pressure of venous congestion of your specific organs, and you're going to get damaged. Your block, your kidneys. So you want to be about here. Where is here? Well, when you find it, let me know. It's kind of the holy Grail of acute medicine, and we're still trying to find it, and that's really all I have to say today. So any questions, I'll be happy to answer. Yeah, Thank you so much, Doctor Google for the absolutely brilliant lecture. I'm sure everybody learns a lot. I'm just posting the feedback for men. So if everyone could please kindly fill this feedback form out, it's really important for us to carry on with these lectures, and I'll let them carry on with the questions and keep the call open for a bit longer. Thank you. I hope you are all safe. I feel very humbled being here with you. By the way, Um, I really I've never been so moved to be such a fantastic group of people. You inspired me. Uh, good question. Uh, from DOREENA. Yeah, I can it be rebuilt? That's a great question. And that's being studied. The early evidence seems to suggest, and this is early evidence that possibly album in and possibly steroids. I think the strongest thing to say is, uh, to prevent damage the glycolax. But the earliest indications are steroids and albumin. But don't you know, don't go running around giving people steroids and albumin based on it yet because it's still early days. But, you know, it kind of makes sense as well, though. But that doesn't mean, it's true to keep an eye on this. Keep an eye on the literature. You'll find that more. And by the way, I just just to recap what I was saying, I sometimes feel it's a little bit. Some people feel a little bit uncomfortable and that I can't give you a black and white answer saying, Do this, Don't do that. Uh, this is the uncertainty that is inherent in medicine, and it makes it may be interesting, but it's, um it can. For some people, it's it's a little bit unsatisfying and that they want, you know, like a cookbook recipe on how to do things. And I'm afraid life isn't always like that, but understanding the principals is really important. Doctor Vogel, I'm just going to come in. It's er Doctor Raymond here. Thank you very much for an excellent lecture. I think we're going to be finishing early. Uh, a moderator will just, uh, post again the link to the feedback. Uh, when you fill in the feedback for me, please remember, uh, it's today's date that we're asking for. And, uh, the lecturer obviously is Dr Vogel. Um, and the topic is, uh, anaesthetics. just one word is fine. I know there's a bit more detail to it, but that will do just so we can identify who's lecture you're feeding back on. But we really, really need your feedback. So will be very helpful to have that. And thank you for taking the time. If there's any issue with the certificate, um, then we will put an email in the chat that you can contact to get help with your certificate if you're not able to see it on the chat. Uh, is it um I can't I'm sorry. I know how to pronounce your name. Is it okay to use diuretics? I couldn't see the rest of the question. So the question is, is it okay to use diuretics when we see that we gave too much fluid to our patient? Like in order to find the sweet, sweet spot? Uh, yeah, that's a good question. A little bit. It's easy to say just yes, but as you'll see in the next couple of lectures, especially the not the next, the next after the next one. Um, there's a way of measuring your fluid responsiveness, and some people are using that to determine when they can start taking fluid off with diuretics, for example. But yeah, diabetics, The short answer is yeah. Yeah, I think so. If you're if you're absolutely certain, Yeah, that you refilled. Okay, if there are no other questions, then we'll end in about a couple of minutes. So please, please fill in the feedback. The certificate will be posted very shortly. And any issues with the certificate, we put an email address that you can contact if you've got certificate issues with the certificate that's in the chat. Thank you, everyone. I think we're still waiting for some more people to complete the feedback, if you possibly can. If there are any issues with the feedback for me, please let us know in the chat. But we do need that feedback. Hello. Hi, Doctor Google. I think there's no more questions coming through for now. I think some people are just talking about the feedback for, um But thank you so so much the wonderful lecture. Um, and I'll keep the call on for a bit, but you're welcome to leave if you've got other things to do. There just I saw there's a guy named Kingsley or someone in Kingsley Who asked, What would I do in the case of a cardiogenic shock and a massive pulmonary edema again, Uh, yeah. I lift the legs and see how they respond. I don't know if they're still here, but, uh, yeah, that's that would be the thing to do. So I can't seem to see that in the chat, but yeah. Okay, well, I'll sign off in that case, and I'll see you all next week. Lovely. Thank you so much. Doctor. I really appreciate your time today. Thank you, everyone. I think we've solved the issue with the feedback for me. You got to put the day, the month and then the day of the month and then the year. It's American style. Thank you for my That's for my benefit. Okay, everybody, please stay. Say bye bye bye now.