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Okay, Let's see. We share a screen here. Uh, no, don't do that. Hello, everybody. Uh, okay. Can everybody hear me? Okay, great. So, um, I'm still Doctor John Bogle, Um, relatively recently retired consultant, Any case consultant in intensive care medicine. And And today, I'm going to talk to you about something we come across quite often in I t u in intensive care. And that is sepsis and septic shock. Very, very topical subject, at least in the UK but not just the UK There is. Um, there's It's always in the headlines because people miss out, some young person dies and so suddenly becomes a a banner headline. So we're gonna talk about septic shock today. So the outline we're going to talk about definitions, the epidemiology pathophysiology diagnosis, treatment, and long term see quickly. There's a lot in. So try and go through this. It's gonna be very relatively superficial. If you're interested in this subject, I have loads of references. I can I can pass on to you. So, definition, What is it? Well, the in 2000 and I think was 14. There was a major international conference to try and come to a consensus on what the definition of sepsis and septic shock was. And they called this the sepsis three definition because there were three, um, uh, situations of this conference. And, uh, so this is a quote unquote major breakthrough. And what they said was, What is sepsis? It's a life threatening organ dysfunction. So it's gonna be life threatening a dysfunction of your organ. And it's due to a dysregulated host response to infections. So it's not the infection. It's the host response to infection. So you're basically, um, over playing your immunology, and this came out in 2016. Interestingly enough, uh, William Osler, who was considered the father of modern medicine in 19 oh, four, said that this was a patient. The patient appears to die from the body's response to infection rather from it. 2016 to 2004. We really haven't learned a lot, have we? And, as they say in French police cassettes change. So what are the sepsis? Three definitions. Quite simply, sepsis is the infection, plus the life threatening organ dysfunction that you're is due to a host. Um, inappropriate reaction to that infection or excessive reaction. Septic shock, which is different to sepsis, which is a subset of sepsis, is whereby you are unresponsive to fluids and you stay hypertensive so you give fluids and you're still BP. Still low your lactate sar high because a sign of either, um, lack of oxygen to the cells or to the stress of the sepsis, probably more likely the second and a BP that requires vasopressors to keep it above the mean arterial pressure above 65. That's their definition, and it's a little bit arbitrary if you look at it carefully. What about epidemiology this? So how common is sepsis? Well, there are various approaches of sepsis in different countries, and I'm just choosing the UK is because that's where I am. It's no better or worse than anybody else's. But in the UK, they have a sepsis trust, and they found that, um, every year there about 50 plus 1000 deaths from sepsis, which is more than bowel, breast and colon cancer combined, which surprises a lot of people because we know about cancers. We know about scheme of heart disease and strokes. But we rarely talk about the problems of sepsis, and you can see here the UK, and this is very similar in other countries. By the way, sepsis is pretty close to ischemic heart disease way above COPD c b A and we just said cancer. In fact, a recent study came out from The Lancet just last week, and they said it was it was a cause of 10 million deaths worldwide and was, uh, implicated in one in five deaths globally. So it's a really major problem, Uh, that which most of us don't really talk much about. So how serious is sepsis? Well, let's look at Let's look at the mortality from a myocardial infarction. Everybody knows how deadly a myocardial infarction can be. So you look at 100 people about roughly Depends on where you are depends on circumstances. But there's a This is a ballpark figure. About one person in 10 will die from a myocardial infarction. So about a 10% mortality all comers X septic shock. Look at the same 100 people, and it turns out it's more like three out of 3 to 4 out of tens of 30 to 40% of people will die from septic shock. So it's a killer. Now there's been recent studies saying that the mortality has dropped dramatically. That's not true. What's happened is that we've expanded the definition of, uh, we expanded our sensitivity to detecting sepsis, so the denominators got bigger. But the actual mortality is pretty similar. Wherever you look in the world, it's about 30 to 40% of people with septic. Chuck will die. What about the pathophysiology? Well, it is really complex, and I will not try. I will not even try attempted to, um, dissect all what's going to happen. I'm gonna try and make this quote unquote simplified, and it's not even that simple. So this is from an article in the New England Journal of Medicine, and you can see there's something called P R. R. That's pattern recognition receptors that you have that are sort of like the common pathway that you, um, you you turn on your immunity to what is called a p pathogen associated molecular pattern, or paps. So these are terms. If you're interested in sepsis, you will come across Paps damps pr are These are just like locks and keys, if you like. So the lock is a PR. Are the pattern recognition receptor and the and the keys are the champs or damps, which are basically bits of necrotic tissue. So you have pancreatitis, for example, without infection that will cause necrotic tissue damps, and that will trigger your P R R. What's important to notice is your trigger is going to is going to unleash pro inflammatory but also anti inflammatory responses. And there's a balance in this, and that's what's so important. And the thing that's really striking is we used to think that one pro inflammatory would be followed by anti inflammatory responses, but it doesn't work out that way. It's it can be simultaneously one after the other. It can be anyway, so it's really complex, and I won't bore you to reading the rest of this slide. But you can see it's quite a complicated, um, a series of reactions that occur. But what's important to notice is that you can get not just a pro inflammatory response, but an excessive inflammation causing collateral damage. Hence that will that will cause the release of damage, cell protein and necrotic cell death, and that will cause deaths, which will also trigger your P R R. And that will carry on the process. The other side of the coin is you can have immuno suppression, and therefore you're more susceptible to secondary infections. You're basically defenseless, if you like against the kind of infections you might come across later on down the down, the down your eye to you stay not just reminding you damps are a big player, so all this is more relevant when you look at the temporal pattern of what happens. So if you come in with sepsis or septic shock, the early phase you have an early phase, a transition in the late phase, so you classically start with hyper inflammation. But again, it can happen. Hyper and hypo inflammation can happen at the same time. It's very difficult to, uh, dissect the weaving I/O of those two, those two, uh, inflammatory patterns. And so you have what we call innate innate immune response. And that's your body's first line of defense against invading pathogens. It's rapid, and it's not specific. So you didn't have to be exposed to the, um, the bacteria beforehand to to to, uh, to launch an antibody attack. So it's basically your first line of defense. But You can also have the immuno, uh, suppression or the Hypo Inflammation response and there that will cause an adaptive immune response. And that is your systems slower response that uses immunological memory. So your T cells, your B cells and the like. Now what happens with your typical patient is you're trying to go from either hyper or hypo and go back to homeostasis to back to normal the imbalance again. And that happens in about 60% of patients who have got who have sepsis, sepsis or septic shock and they recover. So about six out of 10 will recover when they get back into Homo state is to get back into the balance. But in about 10% of patient's, the early phase of this sepsis will cause a massive release of inflammatory mediators, and about 10% of them will die early from this massive inflammation. But about 30% of those patients who do not survive will not die early. They'll die later, and what happens is they go into a hypo inflammatory response, and they are prone to, um, secondary infections later on because they're immuno suppressed and they cannot combat secondary infections and these patient's often die of secondary infections. So the commonest way you're going to die with septic shock if you're going to die, that's about 40. About 30 or 40 out of out of 100 is not due to the massive release of inflammatory side icons. That's about one in 10, um, but about 30 or more percent will die longer. Longer term. We're talking about days or maybe even a week or so from secondary infections, because they're hyper there, immuno suppressed as opposed to hyperimmune. So let's look at the pathophysiology of sepsis a bit more closely here. And this is an ongoing debate, and the question is, what's what's going on with the body when you're getting septic? Septic? Some people say it's the fault of the micro circulation. So what happens is the micro circulation either clamps down so the cells aren't getting the oxygen they require. Or there's, uh, the shunts, so arterial and venule shunts, and so the blood's going past the cells. But it's not actually delivering oxygen. That's one of the, uh, theories. The other is. The mitochondria actually is hibernating, it turns off, and so it's not using oxygen in some ways, it's logical that if your mitochondria is not using oxygen and we know oxygen is toxic, if there's excessive oxygen, it's toxic. So if the mitochondria is not using oxygen, the excess oxygen that's not being utilized by the cells is hanging around outside the cell. And so the micro circulation logically should clamp down because you're not gonna wanna deliver oxygen to a cell that's not using it. So the question is, what comes first? Chicken or egg? Is it the micro circulation not delivering oxygen? Or is it? The economy is not using it. So the micro circulation is reacting as it should do, uh, by not allowing excess oxygen to to, uh, to persist. So which is it? A good question? So what evidence do we have? It's the fault of the mitochondria. Well, lots of studies have looked at this, and they found that in fact, your cells seem to go into what looks like hibernation at the expense of the cells function. It's basically saying, Okay, I'm not going to function. I'm going to sleep like a barren winter, but we're just gonna have to live with that, and in fact, what backs that up is that if you look at patients who have died and you do an autopsy, it's surprising how little cell death is, uh is found despite the profound organ dysfunction. So it's like the cells have gone to sleep to try and protect them from this lack of, uh, well from whatever's causing them to go to sleep, UH, might have come to turn off. And in fact, if you look at this study looking at muscle cells and their ability to produce energy ATP from mitochondrial electron transport teams, you'll see that complex for which is, uh, part vital part of your electron transport chain, which is used to produce energy in the cell in the mitochondria. Um, if you look at the controls in ICU Patient's, that's what a control would look like. And that's what an ICU patient would look like. So you can see that the the energy producing mitochondria is not working because the complex for part of the electron transport chain is turned off. So that's pretty good evidence. But what about the micro circulation? So this is a video of what we called sidestream dark field spectroscopic, and you can see This is some of the septic shock, and you can see they're they're, uh they look terrible if you knew what normal would look like and we've seen this in the past. Lectures. What a normal circulation. Micro circulation looks like. This is someone's micro circulation being resuscitated with glycerol time trinitrate, um, which is one way of opening up your capillaries and you can see the macro hemodynamics are not all that different between the preceding video and this video. But the this the capillary circulation does look a lot a lot better. So again, we don't know which it is which. So which is it? Is it one or is it the other? Well, it depends on your perspective and probably, as they say, somewhere in the middle. But who knows? So how this is this is something practical. This is a very practical slide. I was hesitating putting this in, but I think it's important. Twice in my career of 41 years, I saw two patient's relatively young who we thought were about to die from septic shock. No matter what we did, they were they were not going to survive. And somebody brought up the idea that this could be due to very, very. Barry Barry is a lack of tpp that's thymine pyrophosphate. So stymie vitamin B one. And if you don't have thiamine, if you have Berry Berry, you turn off your cells ability to produce energy. So it's not that common, but it's not that rare, either. And the thing that's dramatic about it is that this berry berry causes fulminant cardiovascular collapse. It's called ocean beriberi. For those that are interested, uh, it creates shock high levels of lactate high doses of as a pressures are required. And, as I said, it resembles septic shock. Exactly. And so what we did in these two cases that we thought were basically, um, going to going to die. Uh, we gave thiamine both these cases I was involved in, and I was really amazing how fast these patients recovered. And it caused an incorrect, dramatic and rapid, um, recovery of your cardiovascular disparity system. So if ever you get somebody who looks like they're about to die or looks like they have septic truck, never forget to give them time. E. How about diagnosis? Okay, so there are various screening tools that you'll have heard of. They're all They're not that great. They're not that sensitive. I think the most important diagnostic tool is to think about this as a diagnosis. And here's just one example of a diagnostic tool that's used in the UK There are many others. Um, they're all as good as each other. Really? Um, this one. They look at various, uh, simple clinical parameters like temperature, respiratory rate, heart rate, etcetera. Then you ask yourself, if these are abnormal, could this be infected? If the answer is no? Well, then it's not present until you go to your standard treatments. If it could be present, then you ask, Is there anything that's particularly a red flag that makes you really worried that this could be a very severe case of sepsis or septic shock? So you look at your BP, your lactate, your extreme and heart rate and respiratory rate saturation, etcetera. And if the answer is no? Well, um, then, um, there's sepsis, but it's not a red flag. Sepsis is not, you know, dramatic. But if it's yes, then you've got a red flag, sepsis, they call it, and then you have to really have you have a time critical condition. You want to get to, you know, get to Axion really quickly. So this is one of many types of screening tool. This is an example. I put this up because, um over the last few years, in fact, this is just one example of many, many, many examples. There have been almost, I don't know. Every month it seems to be there's a headline on the news. In this case, it's the BBC saying that the dramatic case of so and so young man or young woman young woman who was taken to hospital and, um, they were told to go home where they were left in the corner of, uh, an accident emergency department and they found their dead where they die. Soon afterwards, they go home and they come back and they're already dead. Why? Because the patient had sepsis and nobody even noticed it. So what? They always say the same old story every time is the problem with the patient's. When they looked at what happened is they died unnecessarily. That's the key word of sepsis because the staff didn't even think about it. And that's the key factor in this talk. Think about sepsis and they were using guidelines without even thinking. So you got to use your brain and, you know, don't forget to think. Could this be sepsis? And don't forget, this is time critical. If it's if it's if you have a red flag or if you have a severe case of sepsis or septic shock in particular, the clock is running. So minutes count. Okay, how about treatment? Well, this is the sad story that I find for someone who works in intensive care that today we don't have any magic bullet. Yeah, we give antibiotics. That's true. We have some treatments, but essentially today, all we really do is support you until your body decides it's going to survive or it's not. I can be so you know, blunt about it. And one thing is very clear, and this is very disheartening. In the last 40 plus years of intensive care, which I've been involved in, um, we may not be able to make you better, but we definitely can make you a lot worse. And so a lot of the breakthroughs of our treatment in intensive care special regarding sepsis has been that we have discovered things that we've been doing that will cause you harm. So by removing these these harmful effects, we consider an improvement. But we haven't really found anything to make you better. So, for example, the way we ventilate you, um, glucose control, etcetera, etcetera, lots and lots of things that we can talk about which we've discovered have made you worse. So we can't We can't make you better, but we can definitely make you worse, and we try to reduce that. So the question is, why have we had so little progress over the years? And this is probably because if you look at oncology so cancer therapy, they're very, very much in advance of us. So in cancer therapy, what we do is we don't just say you have cancer. We say you have breast cancer. What kind of breast cancer they do a genetic study. They look at receptors. You have a triple receptor negative cancer, negative, triple negative cancer. They call it, um, that has a different treatment, has a different prognosis. So they're really drooling down there, becoming much more granular. And they don't just say when you have cancer. You have breast cancer. What kind of breast cancer do you have? A spread, uh, to lymph nodes. Um, do you have a receptor, uh, pattern that's appropriate for the treatment we're going to offer you. So the really drilling down to the detail what we've done? We've just said you have sepsis receptor job, and we use this umbrella term, which is really very, very impressed. Sized. So as a say, it's just like me saying to you, You have cancer. What treatment are you going to use? Well, you have cancer. So that's what we're at the moment. But we're going to clean down. So how how are we trying to change this? Well, in the last few years, we've decided to use a similar approach to the oncology teams, and that is we're going to use different enrichment. Uh, they call this enrichment. You're going to hear the hear these terms in the future. Prognostic enrichment and predictive enrichment. What does this mean? Well, if you take a group of patients with substance, so they're all different colors, as you can see here heterogeneous. And we say you're septic, like we said, you have cancer. Okay, now we're gonna divide these people up into two groups or several groups, and that is based on your prognostic enrichment. That means what is your likelihood of dying? So we we use what we call, um, risk assessment so your chances of dying may be low. So in that case, you don't have to be too focused and too worried about these patient's because whatever you do, they're probably not going to die. Or you could have patients who are at a high risk, and you have different cut off points and different tools to determine what the risk is. There's something called the a Paki score, which is one of many tools that you can use to define people into high and low risk categories. Now, once you have a higher risk category, that means now you can probably manipulate these patient's to try and use a treatment that's adapted to them. And what they do here is what they call so your standard care for the low risk because there's not a lot that's going to cause them harm. Then the next group you use predictive enrichment, and there you're starting to use things like Transcript oh, mix kinetics proteomics, um, clinical clinical tools that allow you to divide people into different groups. And so you have specific biological mechanisms and like there's, we'll just say Bilek this this very crude example Bio biological mechanism one versus biological mechanism to So, for example, there's one study that looked at people that are hypo versus hyper inflamed using genetic tools. And they found that steroids given to one group causes benefit. But given to the second group, it causes harm. Now imagine we gave steroids in this example to the group on the Extreme left. Give it to everybody. Well, it either is gonna not be seen to do any good at all because we we basically used a blunderbuss approach and we haven't been focused. And that's what we're trying to do now to focus. Okay, so what about initial sepsis management? You've got someone in the accident emergency department, and the very first thing you ask yourself is, could this be sepsis? That's the most important thing you can do. And we talked in one of my earlier lectures about the importance of simplifying patient's, uh, your approach to patient's and just going to the oxygen delivery paradigm Okay, So can I improve oxygen delivery and the three factors we talked about? Cardiac output, hemoglobin and oxygen saturation. So you want to make sure that those three factors are adequate and optimized And because we tend to focus when it comes to sepsis on the cardiovascular system you're gonna look at, how do you manage a hemodynamics and you're gonna give fluid? And there's something called surviving sepsis, which is a campaign that's been around since 2002. And they have every couple of years. They unite a group of experts, they look at evidence, and sadly, the evidence is never very good, and it's somewhat controversial. But that's the kind of model we use today, and they say you give immediately. You give IV fluids, and they usually come out with arbitrary numbers, like 30 mils per kilo of crystalloids and use vasoactive agents. So we essentially talking about nor adrenaline, and you can give them, by the way, uh, they even advised you today to use them in a peripheral intravenous line. You do not need a central line initially in the early stages to give a vaso activation, So this idea that you have to have a central line to give nor adrenaline is not true. At least it's not advised by, uh, by this consortium. Then you've got infection management. And that means what? Antibiotics And depending on the type of steps that you've got and we'll talk about this in a second, you have to give it, um, appropriately. Then you. So you have to make a best guess of what kind of infection this is and what antibiotics to give. And secondly, you want to give it quickly, and the next thing is, of course, source control. And that is vital. You must never forget source control if you don't have control the source of your infection. So so you have an abscess in your abdomen. Then you can give. You can soak somebody in antibiotics all day long. It they won't work. You have to get source control. And then lastly, hopefully some day we'll have a modulation of the host response at the present. We won't we don't really have that. Nothing that really that we do today has been proven to benefit Patient's by modifying their host response, and I put down hydrocortisone because that's a very controversial topic. That's that's That's a more kind of blunderbuss approach. But a more personalized approach is being talked about more often, and this is a cardiovascular approach or hemodynamic approach, so they use something called S O S. D. And that's a different phases of someone's illness when they come in with sepsis. Receptive shock. You want to look at 34 phases the salvage phase. That's your You just come in and you're you're needing resuscitation, optimize. You want to optimize that person, you resuscitate him, and you're beginning to resuscitate him. Now you're gonna try and just get them just balanced. Then you want to stabilize them and you want to deescalate. And I'm gonna go briefly through these goals of you for these stages and the treatments you want to offer them and how you want to monitor them. So with salvage, you want to make sure that the tissue profusion is compatible with life, so that really is a A rescue therapy. You want to use fluids, and you want to base them on the mean arterial pressure usually say above 65. You want to look at the capillary capillary refill time. That's a very very important tool because it's very simple to do. It's gonna be standardized. Um, so you do it the same way with all the members of your team, Um, you want to look at lactate and possibly echocardiography? Uh, vasopressors is another tool you might want to use, And that would be if you're mean. Arterial pressure is not responding to fluids. So if it's not above 65 importantly, the diastolic pressure and I'll talk to you about that in the end because I think that's a really important parameter to to focus on optimize Well, now you want to make sure that the profusion is optimal and that the profusion, pressure and cardiac output is making sure the organs are able to, um to function normally because they're getting the optimum flow to them. And so you want to now focus your fluids not just poor fluids in, but you want to use tests that dynamic tests that determine whether you are going to respond to fluid or not. And that's called fluid responsiveness. And we talked about that in one of my previous lectures. Um, these are dynamic tests, and you want to also assess flu tissue profusion. And again, you want to look at things like mean arterial pressure and C R t computer refill. Time and again, you might want to use inotrope. See if if the person is not responding to fluid, but they still don't have an adequate perfusion, it might be their heart's not functioning normally. And so you want to look at things like Echo or possibly two super fusion monitors like CRT again and focus on inotropes that might be drugs like dobutamine. And then you get to the latter two phases, which are stabilizing and deescalating, and you're trying now to prevent the complications that are associated with the treatments you've offered beforehand. So if you poured in fluids, you often get someone who's quite a dermatitis and has high venous pressures, so they might get, um, venous congestion. And so you're gonna wanna now to start seeing if you can start deescalating by taking some of the fluid away and maybe reducing the vasoactive support, which has side effects as well. So you do want to use them early on, but then you want to sort of take your foot off the accelerator a bit, and so you want to, You know, look at things like, uh, you know, signs of Venus, uh, congestion and or Dema and decide whether I'm going to start removing fluid and reducing my visa pressures. So this is the kind of sequence of treatments you might offer someone's hemodynamic system. And remember, this is important that you will correct the the macro Hema genetics, and this is a very important prerequisite, but it's not enough. You also have to consider the micro circulation, and I showed you the slide in the past, which is a very interesting slide if you measure skin flow. And they did this in this study using, uh, laser Dopplers. That's what a volunteers skin flow would look like based on these, uh, these tools. And if you have someone who's come in septic shock and, uh, has in circulatory shock, not septic shock circulatory truck. Look at the survivors and they come in. The baseline is very low compared to volunteers, but as their resuscitated, they're improving their skin flow over hours. Those are 24 hours, 48 hours, etcetera. What about the non survivors? The non survivors didn't improve. In fact, they got slightly worse, but they didn't improve. And that's the key thing. But was really striking about this study was that both groups of survivors and non survivors after resuscitation had normal systemic chemo dynamics. The BP came up and, uh, the C, D, P. And all the things you'd monitored came back to normal. And yet they're flow peripheral flows. We're not we're not equal. And those that, uh, survived improved their peripheral flows. And how would you monitor this while things like capillary refill time And so how can you compare, say, can put completely refill times C R t to lactate, which is another thing we often target. I use both, actually. So what happens if you look at one important study? If you look at time over days, what happened to lactate and what happened to mortality? You can see that lactate and C R t are pretty pretty similar, so you can use your capillary refill. Time doesn't. It's not expensive, and you can follow that and you can try and resuscitate somebody and try to aim for an improvement to a C. R T. Uh, usually less than three seconds or so. But you want to look at the dynamics of it, See if it's improved. OK, Antibiotics. This is, um, one that we always talk about. So with antibiotics, you've got to be on. First of all, don't forget source control. I have to emphasize source control. You can soak somebody in antibiotics all day long. If they don't have a control. Their source? That could be like an abscess. You're not. You're not gonna get anywhere. You're not going to improve them. But let's assume you've already managed source control. Now you're gonna get onto antibiotics, or you're gonna do it at the same time. Antibiotics and source control. Uh, you got to be on time so early and on target. So you got to accuse. Guess you don't know what the microorganism is. You're gonna have to make an educated guess, but the problem is here you have a conflict of interest. What do I mean by that? Well, we we they emphasized the importance of giving early antibiotics and appropriate antibiotics. No one disputes that some of it's a little bit controversial as the timing, but I think on the whole we agree with that. But the other side of the coin is we're hearing the W. H. O is saying that we're going to run out of antibiotics because of an increase in resistant organisms that are appearing worldwide. And they'll come a day when we won't have antibiotics because all the all the microorganisms will be resistant. So you don't want to overuse your antibiotics. So somehow you've got this conflict where you want to use antibiotics early. On the other hand, um, you don't want to miss use them because you're going to create problems down the road. So you want timely antibiotics versus stewardship, so don't don't abuse your antibiotics. So what about antibiotics that are on time and on target? What happens if you give the wrong antibiotics? You make a guess, and it's the wrong guess. Well, if you do, first of all, that seem to be about one in five times even more. I'd say that we give the antibiotics that are inappropriate, and you can see if you gave the inappropriate antibiotics versus appropriate antibiotics, you're going to have five times greater chance of dying or five times greater chance of surviving rather if you give the right antibiotic. So it's important to make an educated guess. How do you guess? Well, there are various risk factors. You can look at that. You have to know your local ecology. What do you likely to come across? What are the resistant patterns in your hospital, your local, your local environment? It's a whole subject in itself. And what about the delay in antibiotics? Unless there's a little bit more controversial? I think nobody would argue that septic shock so shock with sepsis. Uh, timing is important. You want to get your antibiotics in as quickly as possible. And in this study they looked at patients with septic shock, and they found that, um, for every hour you delayed, you had an increase of mortality by about 8%. Now this study is highly cited, so 8% more people will die with each hours. Delay The problem with this study, like many others, their observation all and some of it. It's a little bit controversial, but I think the consensus is with septic shock. You want to get your antibiotics in within an hour. If it's sepsis and you're not really, you know, they're not in shock. I think you can take a little bit more time to assess whether this really is an infection or not, because the problem is if you just as a knee jerk reflex poor and antibiotics, you're going to get resistance down the line and you're not going to necessarily improve outcomes. So if you're in septic shock, it's a medical emergency. Get your antibiotics in within the hour. If it's sepsis, you have a little bit more time to play with. And this is where I want to talk about the diastolic BP. I find this is a a parameter that so many of my colleagues just ignore. They look at someone, you walk into a room and there's BP on the on the screen on the monitor and they'll say, Oh, the BP is 105 over 38 mean arterial pressure is 66 everybody's happy with that. And I go to my colleagues and say money off of my junior colleagues and say, Does that look okay to you? And I said, Yeah, yeah, you know, Look, there's the mean arterial is over 65. OK, magic number, I say. What do you think? What's your BP Oh, it's 1 20/80. So 38 That's a bit low, isn't it? So the diastolic pressure could be a really, really important tool to help you decide. So how What is the diastolic pressure? How? What determines the diastolic pressure? It depends on two things. It depends on your total peripheral. Resist. So how you know how vasoconstricted you are, and it depends on your heart rate. So here is someone's BP. At 60 beats a minute, the top is a systolic. Yeah, that little dicrotic not tricks halfway down. And then you have the diastolic pressure at the bottom. You want to think of it as a ski slope. It's like you have someone at the top of a mountain and you can ski down for, um, well for a second for one second, and I'll see how far down they can go. And if your vasoconstricted your ski slope is less steep, so you're not going to go down very far. If it's vaso dilated, the ski slope becomes very steep, and so you go down a lot farther. Okay, so there's someone who's vaso dilated. So what happens to your diastolic pressure? It drops. And by the way, the obstacles. If I were to remove blood from you and continually remove blood on you from you and measure your BP continually, the very, very first thing you're gonna see is not your systolic pressure altering. You're gonna see your diastolic pressure going up. Why? Because you're vasoconstricting the opposite of vasodilating. And when someone's got sepsis, one of the very first things you see is they dilate. So if you see somebody comes into the accent emergency department and they have a a low diastolic pressure, I would say immediately this person has sepsis until proven otherwise. So that's a really I find that's a really good, um, tool to help me decide how urgent this patient's care needs to be if they if I think they have sepsis, so look for a low diastolic pressure. The other aspect of diastolic pressure that will. The other thing that will influence diastolic pressure is your heart rate. So how long do you have to go down that slope? So imagine the ski slope again. Imagine it's got a fixed slope. Well, the slower the heart rate, the longer I have to go down so lower my diastolic pressure. The faster my heart rate, the less time I have to go down. So if I have a heart rate, that's 100 beats a minute. My diastolic pressure goes up and a quick clinical story. Many years ago, I was involved with, uh, we had a mortality and morbidity meeting with our pediatric department. Um, I wasn't part of pediatrics, and they told us a story about a young girl, 10 years old who was unwell for about 2, 2.5 days and they didn't know what was wrong with her. They took her to the CT scan and in the scan, he had a cardiac arrest and they could not. They couldn't recover. He died. Very, very sad story. She was previously healthy, and they then killed us all the various, um, cardiovascular parameters on the screen. And nobody had noticed that for about a day and a half, almost two days. Her diastolic pressure was really low. They didn't even notice it. And the thing that also struck me was actually had a very fast heart rate, which means the fast heart rate would raise your diastolic pressure. So her diastolic pressure was low in absolute terms, but with a fast heart rate, that means it raises it. So that means it's even lower. Which meant that this woman, this girl, was massively vasodilate ID and given her, you know, context that can only be sepsis, and they didn't even pick that up. So always look at your diastolic pressure. How about long term sequelae? Well, sadly, if you survive sepsis, everything is not OK. The the long time outlooks are not that great. You have about a three times increase in moderate to severe cognitive and physical impairment. In fact, if you look at someone's, um, cognitive impairment where you even do MRI scans on them afterwards, you find that many of them almost half of them have what would be considered mild Alzheimer's disease. And these are people that didn't have also Alzheimer's disease beforehand and have recovered Septic patient's. About 40% will be dead in four years, and about 80% will be dead in eight years. So the outcomes are not that great. And you look here what this graph of cumulative survival and there been loads of studies all saying the same thing over years over decades. Even these are controls someone for the same age and the same comorbidities and someone who had an infection. In this case, it's a respiratory infection. But other studies look to other infections, and they're the same. Your cancer surviving, uh, are somewhat limited. Long term minutes. So to recap, what we've talked about today, sepsis is common. It's it's much more common than you think. It's the second or third biggest killer, and yet we often don't even think about it. It's deadly. 30 or 40% of patients with septic shock will die. It's often missed, and that's the key thing. We don't even think about it, so do the basics and do them well and do them quickly. You've got to be Johnny on the spot. You got to be quick. You got to get your cultures in early Quickly. You want to get your cardiovascular resuscitation in quickly. Get that fluid in quickly. If you think you need it, the diastolic pressure is low. That means there's massively vassal dilated. If they don't increase their BP very quickly, get a peripheral IV in and start them on, nor adrenaline. Don't be afraid you can use no adrenaline with a peripheral IV. You don't need a central line, but you've got to resuscitate the cardiovascular system quickly. You've got to get source control. You antibiotics do not work if you don't have control of the source of the infection and you want to use early and appropriate antibiotics if you get early antibiotics in. But they're they're not. You take a you don't guess correctly. You don't get the right antibiotics in. You won't. You won't help your patient. So think sepsis. And don't forget to look at the diastolic blood trick. That's my tip to you. And that's really all I have to say about that. Any questions? Hi, Doctor. Uh, hello. Sorry, I I just I just missed that slide with, uh, you know, uh, the slide about the IV fluids, Uh, the slide about the IV fluids? Yeah, that one. This one. The one above the one above this one? Yes. Yes. Please. Yeah. Um, OK, that's quite simple, actually. Um, so I can get onto this? Yeah. So this is just saying, as a sort of general, uh, general approach to someone who's got sepsis or septic shock. You wanna. As I said, this is my take on this. You gave you a talk on when you have something that's very confusing, whether it's a traumatic, you have trauma, where you have someone with severe sepsis and you know you just don't know where to start because there's so many things happening at once. Simplify things, say to yourself, What am I going to try and achieve? It's improving or optimizing my oxygen delivery. And that means I want to make sure my cardiac output is good by hemoglobin is adequate and my oxygen saturation is good. If those three are okay, you're okay. So with this sepsis, they tend to focus on cardiac output, and they tend to ignore hemoglobin and oxygen saturation. I think you have to look at all three, but let's focus on on cardiac output where they say initially, when you come in, you have like a medical emergency on your hands. You want to get IV fluids and crystalloids quickly, and they say again, it's arbitrary. They say about about two leaders for someone 70 kg. OK, pour it in. And if the BP doesn't come up, if they don't improve their profusion number C R t you you feel how cold they are And you look how long it takes them to wreak capillaries to refill. Uh, if they don't improve quickly, then you get a peripheral intravenous line in and you give them nor adrenaline to get their BP up. Then after that, you also at the same time, you have to think about infection management, antibiotics and source control. And I said the third one, I'm kind of hesitating on because we don't really have a way today of model modulating your response to hyper or hypo inflammation. But that will come someday. Is that okay? Yes, doctor. So we give IV fluids. How much you said, Please. Well, that's interesting, because when you come in initially, if you're very unwell, they say to give 30 mils per kilo of crystalloid, that comes to about two leaders to somebody who's you know who's 70 kg. Um, how they figured that number out. I don't know, uh, it's been considered controversial, but it seems to me not totally unreasonable, but it's not. It's not. There's no magic number to it. But what is important is that if you're a person doesn't improve rapidly with the fluids. Then you want to start thinking early to get intravenous? Uh, vasoactive agency, Like, nor adrenaline. Yes. OK, so we we we we give him nor adrenal and the, uh, peripheral. Uh, yeah, well, the thing is that until recently, people always said you had to have a central line to give your adrenaline. And we know from many, many, many studies today that that's not true. You got to be careful, of course, but you can give it if you're careful and you give it into a big nice, you know, fast, fast, fast flowing vein. And you keep an eye on the vein and you don't keep it in for weeks. You keep it in for a day or two. Um, then, um then that's fine. You can do that. It's far better doing that early than waiting to put a central line and then give you your adrenaline so you can use a peripheral line. Okay. Thank you so much. Any other questions? Uh, yes. Regarding, uh, you said that we have to do the culture as fast as possible, But sometimes culture takes a very long time. So is it possible that when we know that there's a bacterial or a viral infection or which is causing the Subsys, mostly the bacterial one, we can use the, uh as fast as we can, how we use the like in today's time. We use the covid test. We checked. The protein is the i G i g m. And we could on those on those basis, we could just identify that. Okay, there is something, uh, bacterial success possible so we could use. Is it possible to use that? Because if it be a very emergency situation, like a septic shock or something, is it possible to be that because culture might take a lot of time? Yeah, a really long time. When I when I said culture, I didn't mean take cultures and wait for the result. That's not what I'm saying. I'm saying, Take the culture at the same time. You're starting your antibiotics. You know, don't Don't forget to take cultures because it makes it a lot easier in a couple of days to get the results back and saying, Yeah, you're taking a You're making a guess. You don't know what the person has If he has a bacterial infection. If he does. First of all, viral infections aren't many viral infections you can actually treat. But bacterial infections you can So you're having to do is taking a best guess. If someone is young and they have, say, a pneumonia, you might think Okay, this is likely to be a streptococcal pneumonia. Um, pneumonia, pneumonia. If you have someone who looks like they have meningitis, well, then you have to go through the various, um, possibilities. Given their age and their comorbidities. It's, you know, it's it's really there's a whole lecture on this. If you really wanted it, I mean, it's a it's a it's a major topic. The good news is there are more and more PCR. Um, you know, uh, genetic studies, if you like, they're going to give us rapid results that are not perfect, but they're going to help us, uh, make a much more a much more rapid, educated guess. But you're right. You don't wanna You're not waiting. No one's saying waiting for for your culture results. Everything. Get the cultures off, and then you basically give your antibiotics and then you wait for a couple of days for your culture to come back. Uh, do we also use diuretics while giving the air fluid IV fluid direct. Well, you've got someone who's basic. I don't see the logic of that. If you have somebody who's, um because in, uh, some of them, like when we had a infectious disease class, Uh, we used to call it as a detoxification detoxification in which, if there is a sepsis, uh, you give the IV fluid and let the kidney, uh, filter the filter, these things which should not be in the body in that manner. Well, no. Well, not really. Where you would use on the fluid. You see the slide I had put up here where it says deescalate. Yes, sir. Yeah. So what they're saying is, when you start to resuscitate somebody, we often poor in fluids, we often mobilize fluids. They eventually over a couple of days, become quite a de metis that causes problems in itself. So what you want to do is then you want to start thinking of getting that fluid off of them and to deescalate. And that means, you know, maybe then you want to use diuretics, but using diuretics to flush out the toxins. I don't think there's any evidence for that at all. How often? How often this is misdiagnosed sepsis, like with something else. And uh, that's a good question. So how often do you think you have sepsis and you don't? Yeah, I'd say probably about half the time. It's It's common, it's not. It's very common, but I think you're gonna. You're gonna cause more harm by under treating than over treating. The problem we've had today is most people don't even think about it. They go into the accident emergency department, and the doctor sees them, and they don't even think that it may be sepsis. That's the thing. It's very common. It's deadly, and most of the time that we we do badly. It's because we haven't even thought about it. That's that's the if there's one message in this in this talk, think sepsis. Is it possible that the people or the geographical conditions might also, uh, cause the diagnosis of MS diagnosis of the substances, such as speaking for a people for a hospital or a small clinic in a developed country, or countries that compared to the hospital in a tropical area or in a developing country might have more cases of substance. That's one of the reasons in developed countries, the substances most overlooked. Uh, you know, that's a good question. I, um uh, it could well be there's, you know, the, uh, in developed countries. We probably assume that, you know more likely to get sepsis and underdeveloped countries. The microorganisms are different. The resistant patterns are very different. Um, but, uh, everywhere in the world right now, there was a very good paper recently in the Lancet looking at the entire world, and it's pretty common everywhere, actually. You know, it's about the third commonest cause of death everywhere, not just in, you know, developed or underdeveloped. The patterns you're seeing, maybe we will be different. Um, but, uh, you know, you just got to think about it, you know, that's the thing. And I think what makes what makes the sepsis part more dangerous is if, like, we're treating the patient with some all a patient who came for some other reason in the hospital, not by sepsis. And if is it possible that the, uh, nose, a common infection, might cause sepsis, then it would be more dangerous, I guess, Uh, the patient then the doctors might think, Oh, this is something else. This, uh, this is a reappearing of the previous disease or previous condition. Well, yeah, I think if somebody if somebody is being treated for sepsis because you've made that presumptive diagnosis and they're not getting better, I think you've got to ask yourself, Is there a source that I'm missing? You might ask yourself, Is this really sepsis? This could be like, is it, uh, it was in Ophelia. Pneumonia or, uh, an organizing pneumonia, whereas or you know, somebody pancreatitis when it's not sepsis. You're right. You know you want to. But the initial approach is to the worst thing is to have someone who turns out he does have sepsis, and you haven't even started treating them because you can always back off. You can always, you know, take, you know, stop giving your antibiotics if it's not sepsis. But if he has got sepsis and you don't give it, they could well die, and then you'll be, you know, Sorry, I didn't, you know, missed out on that. That's the problem. It's very common. Thank you. Anybody else? Um There are a few questions in the chat. It's just we have another lecture starting in a few minutes. So, um Well, uh, I can take a picture and send it to you, and maybe we can You can go over the next time. Okay. That's good. Uh, sorry about that. No, no problem. But, um, thank you very much, as always. Um, and thank you. Everyone who attended. Um, please do fill in the feedback form and really any feedback that you have. Um, we really appreciate it. If you want to say something about this lecture, if you have any specific feedback you'd like to share with us, um, you can write it in the chat here, or you can write it on the WhatsApp group, or you can email us. Um, but yeah, let us know what you think. Um, so I'll give everyone a chance to do the feedback quickly, and I'll end the meeting in about two minutes. Thank you very much. Okay. Is that it? Um, yeah, thank you very much. Okay. Well, thank you. Have a good day. You too. Thank you. The certificate is in the chat. Um, if you can download it. Uh oh. No. Sorry. 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