Hi. Thanks for joining me. So I'm Chloe Fay, and we're gonna talk everything about the septic patient.
This is a real passion of mine, this topic. And weirdly, we kind of see a lot of septic patients in at the hospital that I currently work at, and whether that's just because we've got better at looking at the the biomarkers and the diagnostics and picking up on it earlier or whether it's just because we're just seeing a higher number of patients that are separated for whatever reason. OK, so if we think about sepsis and what is sepsis, it's very broad.
There's lots of definitions out there, but basically the sepsis definitions are defined in human medicine. And hopefully well, most recently, there has been some definitions released by a group, a veterinary consensus group, and hopefully that will lead on to further definitions, bundles, treatment and kind of protocols that are more veterinary specific. So veterinary is a major cause cause of morbidity and mortality in both human and veterinary medicine.
And it is that life threatening condition and the reason why they get this is this. But the body is dysregulated in a response to an infection. And so this is the specific, kind of, definition, in the most recent se surviving sepsis guidelines.
And that's a dysregulated inflammatory response to infection or to trauma. And so what happens normally is that the body releases these chemicals into the bloodstream. They fighting and and they're normally just fighting that, infection.
Locally. What happens in sepsis is when, this body response to these chemicals, is out of balance, and that triggers changes that can damage multiple organ systems. So it's true definition, as I've just put here, is this disregulation.
So we have both pro and anti inflammatory responses to this infection or trauma, and what we see is a progressive kind of organic slow, progression, and that causes multiple vital organ failure. And that is also coupled with critical reduction in tissue infusion. So within sepsis, we also have further definitions like septic shock.
And we'll talk a little bit about SARS as well that systemic inflammatory response syndrome. So I just mentioned the surviving sepsis guidelines. The surviving sepsis guidelines is a consensus group, and they started out, way back, in like 2003, and they kind of had this definition actually started in 1996.
But as they grew, these definitions changed. And the most recent, as I said, those in, 2021 is this dis regulated inflammatory response to infection and trauma. And again when we look at our surviving sepsis, kind of guidelines that are now coming about in veterinary medicine, there's a slight difference.
But again, looking at the evidence, and all people are evaluated as well, so they kind of recognise that sepsis is a primary cause of death from infection. Especially if it's not treated or recognised, promptly. And once we recognise that, that patient has sepsis, is that that mandates urgent attention.
And this kind of pathway of sepsis is shaped by a lot of pathogen bacter, which we'll kind of just touch on today is very deep in in pathogenesis, and very heavy on pathogenesis. So I'm not gonna go too much into it. More to talk about today about the bundles, our diagnostic markers and how we're gonna measure measure our progression or, deterioration in our patients.
And so it's also dependent on a lot of host factors. And character evolve over time as well. And that might be age, sex.
And then so for humans again, like race, genetic determinants, comorbidities and environment. So these again, some of these are applicable to our patients. But what differentiates sepsis?
From an infection. Is this dis regulated host response? And the presence of organ dysfunction.
So those coupled together are what makes sepsis? As as our diagnosis. So when we're thinking about I'm at this kind of surviving sepsis guideline, this definition of sepsis, often the systemic inflammatory response syndrome has kind of been bandied about.
And, in previous years, there was a heavy kind of focus on that. Those patients must meet this systemic inflammatory response syndrome. And if they met all these, and their likelihood is that they were, you know, had some element of sepsis.
So the human guidelines have kind of moved away from this and again. The veterinary guidelines, the the newest ones that have just been released at JVC in the last month or so, and were presented at EE were that? Yes.
Systemic inflammatory response syndrome is a great kind of trigger for us to think. Stop thinking about sepsis and and start putting these patients on septic watch, and thinking about the fact that when we have this systemic inflammatory response, that this clinical condition is caused by widespread activation of the inflammatory system. So we are having an element of that, dysregulated response to a host infection.
But it also might be secondary to a sterile inflammatory disease. Infectious insult. If you think about a lot of patients that we have in the hospital and you look at this kind of chart here, a lot of our patients will fit into this C as well.
They they'll fit into the two criteria required for dogs or three criteria required for cats. And so, whilst it is a useful tool, it's not the only tool that we're using to kind of look and assess with our patients and have an element of sepsis and present and so kind of What? The caveat is that is that we use this, but we again we think about, when we go back to this kind of definition as as a response to collection or trauma.
So thinking about, history of your patients and thinking about whether these patients have, something that might cause, an infectious insult whether they have, a trauma that's caused that activation of that inflammatory system and that this regulated response, to that trauma. So thinking about whether you know, potentially, this patient has pyelonephritis Do they have, endocarditis? Those those kind of things are gonna trigger us and make us think about Does this patient have a higher risk of developing sepsis?
When we think about our immune response and how that normally happens on a cellular level, we're just gonna gonna briefly go over this. Our immune response to pathogens normally will just trigger local reactions that, with time, become, systemic if necessary. So when we have this locally, controlled infection, this host defence mechanism can become detrimental when we activate it systemically so on a smaller level.
Great. These, these macrophages and neutrophils T cells, B cells all do what they should do. They keep this immune homeostasis and kind of go in.
They find, find cytose any, infectious, material. Any bacteria get rid of that on a local level. Again.
Any trauma? They they get rid of any, debris and as such and, is kind of done with this septic reaction. The the systemic activation of these, pathogens is gonna travel via the vascular system.
It's gonna spread inflammation throughout the body. And that's gonna lead to organ failure. Because what we see is these damage associated molecular patterns, these damps and these, pathogen associated molecular patterns, these pumps, and as well as that, what we get is these, neutrophil neutrophil extra extracellular traps.
So they kind of work as nets that they, you know, they they're called nets. They work as nets to try and trap, kind of bacteria. And on a local level that, works perfectly.
If you're doing this widespread, you're gonna start to widen this neck, so to speak. And you're gonna grab anything even if it's not a patho, you know, pathogen. And the other thing that happens is that we get this, sequential, triggering system.
And that what leads to inflammatory cytokines as well so early infections represent this race between the ability of the pathogens to multiply and spread versus the host ability to kind of sequester and kill these pathogens before they disseminate around the body. So this pathway begins by the pa, the immune cells. So these T cells and B cells, they trigger toll like receptors.
So toll like receptor a toll? Toll receptor four is the most common that we see are activated in sepsis. And what they do is these recognised pathogens.
So these, pathogen associated molecular patterns. They kind of pick up on these pathogens, to remove them. Basically, and this leads to local vasodilation increased vascular permeability.
And that goes hand in hand with that recruitment of neutrophils monocytes, to to phagocytose those pathogens and get rid of them. And then the local cardiopathy as well to kind of allow for those pathogens to be phagocytose and removed by those neutrophils macrophages, and so on and so forth. So, obviously, on a larger scale on our patients on this, systemic activation, we don't want our patients to have coagulator, coagulate, kind of disorders because our patients are now going to start to bleed out.
They might potentially be hypercoagulable. So we might be throwing plots. Like, we see with, thrombo.
You know, our our thromboembolism. We don't want, these pathogens associated molecular patterns or these, damage associated molecular patterns going around and, getting rid of all the cells. Because then they don't They're no longer, specifically looking for those pathogens.
They're now just removing anything that they find. As such and again, what was local vasodilation and local increased vascular peril is now widespread. And this is when we start to see our patients getting things like septic shock.
So the septic shock definition is that we have a patient that has increased vascular probability. So now, you know, the vessels are no longer able to retain, their volume. And what we see is we can start to give our shock bola thing.
Because we recognise the cardiovascular system, is depleting as we do with things like hypovolemic shock. But unlike obviously hypovolemic shock, where we've had an actual like loss from, say, a trauma because we have this vascular permeability. We just have this kind of, this leaking out.
And so now what we need to do in our septic shock if we're given bolics and we're not seeing any improvement, we have this non responsive, this non fluid, responsive shock. We now start to think about vasopressor. And we'll talk a little bit about that later when we think about fluid choices and and where our patients are at.
So I mentioned these pumps and damps. And what happens? We get this, with our histones, that we see we get these this pro inflammatory response.
And what happens is this becomes cytotoxic. So we get this histone administration and that causes that neutrophil migration to come to wherever normally, where would be a local inflammatory response, and now is a systemic we get endothelial injury and dysfunction. So again, we know that our glycolic in, sepsis is affected.
Often we can see haemorrhage or thrombosis if we've got, coagulopathy, coagulopathy involved as well. And so when we have these pumps and dumps, what happens? We have these, resident and recruited antigens, presenting themselves these a P CS such as macrophages.
And they alert that hosts the presence of infection. Through these P these pa, pathogen associated molecular patterns. So they kind of pick up on, these pathogens through It's almost like a computer system.
They, are processing them. So they recognise these pathogen recognition receptors as PE PR RS, on the macrophage, they live on the macrophage. And what they do is they respond by secreting cytokines and that contribute to that innate inflammatory response.
So these pathogen recognition receptors on our, on our a PC So I looked on our macrophages and our toll like receptors. As they're processing these, they recognise a range of bacterial cell wall lipoproteins, lipo polysaccharides as well as, other things like fungal wall elements. And, viral nucleic acids.
They recognise a lot of pathogens, that the body might see at some point. And what happens is this immune response is triggered by these receptors because they pick up that these are foreign objects basically within, within the body. And so they sense those bacterial products or damaged cell derived products.
So, those cells that have been damaged by the pathogen already So there's damage associated molecular patterns. Those damps will pick up any damage that those, pathogens have left in their wake. And so, by doing that, they've picked up and they kind of trigger this response this kind of pathway where these cytokines are now released, and initiate this pro inflammatory response as a mechanism of defence.
And so the cells of the immune system, will again use lots of these pattern recognition, receptors that detect danger. And they mount that specific immune response which we'll kind of talk about now. But what we see is this excessive cytokine production and those, the systemic inflammatory response syndrome, which we just saw the table for, as this is what we see as a result of the systemic inflammatory response syndrome happening in the background.
So, most importantly, is kind of this cytokine storm that happens as a result of our damps and pumps and our toll like receptors as well. And so, as I said, there's histones, that are kind of produced. They result in high levels of cytokines.
Like, interleukin six interleukin 10. Tumour necrosis factor Alpha. And so all these, you know, these sidelines are released, and what happens normally, is that that the sidelines will basically come.
And, they kind of repair damaged tissue or fight pathogens. And they travel to the site of infection. And so, as well as releasing those, like tumour crosis factor Alpha, though the response also generates anti-inflammatory cytokines, soluble receptors and receptor agonist for cytokines as well to kind of limit, their production and activity to that local response.
But in our septic patients, and when that immune system is fighting pathogens or repairing the damaged tissue there prone inflammatory cytokines signal immune cells such as T cells and macrophages, which we know are going to travel to the site of infection. They're going to cause fy Tosis. But now what we see in this cytokine storm, and we get this excessive production of pro inflammatory cytokines.
And rather than being selective about the infected cell that they're now gonna fibro cytose and get rid of they now are not gonna be, selective and they're gonna get rid of every cell that they that they see and that is obviously damaging to our patients. And this is why we have endothelial damage that the like of Cali is damaged. We get that multiple organ dysfunction and death as well.
And in addition to those macrophages and T cells being kind of called to the site of infection, the cytokines also activate these recruited immune cells, and to bring more cytokines, basically. So it's kind of like, a vicious cycle in that the more cytokines that are there, the more that they're going to signal to recruit more immune cells, which are gonna produce more cytokines and on and so forth. So this is just kind of a big ball rolling down the hill and gathering things as it keeps going.
So it's our patients are only gonna get worse and unfortunately, deteriorate and, in a lot of cases die. And this is where we kind of come in and and thinking about our biomarkers, our diagnostics, how we can create our own veterinary treatment bundles, and thinking about early goal directed therapy. So this is just kind of like, I'm I This isn't necessarily always gonna happen in this order, this flow chart.
But this is just kind of an idea of what happens. We get the sepsis, we get those activation of the neutrophils. Again, those, we get from neutrophils, we get the release of histones through the through the pathogen.
Receptor. There's PR. R.
There's, pathogen recognition receptors. With that, we're gonna get our cytokines released. And that's kind of gonna end up being like a vicious circle.
So we get back, we get more neutrophils more, more macrophages being released again. Activation of plates. Platelets.
We know our coagulation system, gets activated. So our platelets are gonna be activated. We're gonna potentially have, signs of thrombosis.
If we're having an excessive amount of platelets being activated again, that coagulation cascade. We're gonna start using all those factors, and eventually we might lead to things like disseminated intravascular coagulation. And that's because we get that hypercoagulable phase.
And then that hypocoagulable phase where our patients start to kind of bleed out. And this activation of population kind of goes hand in hand with that septic shock. We know those vessels and septic shock are leaky.
We have the vascular increased vascular permeability. We have, activation of the endothelium. So we get pary leaks and edoema formation.
So we get loss of proteins, loss of fluid. Again, there's neutrophil extracellular traps, and those nets again are gonna, contribute to fibrin formation because they create this net. They're now catching all the fibrin.
They're catching all the platelets they're causing F development, which is in some cases, is great. But in other cases, when we have this, now we start to see a prothrombotic phase. We're seeing lots of clots everywhere.
And that might be a pulmonary thromboembolism. That might be, an arterial thromboembolism. And, you know, and and this is when we talk about our clinical signs and and what we're seeing in our patients, and and another reason why our patients lead to organ failure, because if you if you have a prothrombotic phase and your patient is now getting clots, in the kidney, we lead to things like acute kidney injury, which is only gonna get worse if we're not providing, treatment to that patients to try and reverse that acute kidney injury.
And so we start to see kidney failure again, lack of oxygen to, and circulation to our major body organs. Is gonna happen, because again of this, leaky ve these leaky vessels that, profuse, peripheral vaso dilation, and the edoema formation, you know, the loss of protein so the fluid isn't being held in that intravascular space. It's not reaching those places.
And we know that the shock especially, it is, this patient isn't getting enough oxygen. They're hy I'm hypoxic, in those tissues. So when we think about this kind of flow chart in our early stages of, septic shock, what we often see is this hyperdynamic phase, and this is kind of that textbook that you might know about.
As as patients may show that they have dark red mucus membranes and, a short pary refill time. So less than one second, they might have an elevated heart and respiratory rate as well as pyrexia. And when we think about why that is, that's because, of the, because of the shock that you know, the septic shock, that they have, and their vessel, their vessels are leaking.
The they have vasodilation. I'm not able to pump that blood around, effectively. So the heart works a lot harder to try and keep that cardiac output at, up.
So when we start to see in our, in our kind of later stages, once we start to move through those bounding pulses and the signs kind of associated with peripheral vaser dilation So initially, you might see that, that increase or normal blood pressure but we start seeing these advanced stages is that the mucus membranes might seem kind of grey and very dry increase reasonable time and weak pulses. And that's because that blood is being redirected. And so major major body organs to try and keep that patient alive and again, we're gonna have dull Lation at this point, and I will just say as well, kind of with the caveat that the dark red mucous membranes is kind of our textbook, like our brick red mucous membranes is a, kind of a sign that we all know about when we think about sepsis.
But if you think about patients, especially with patients with septic shock and when we think about shock, meaning that these patients are hypoxic at tissue level, is that they sometimes are pale and therefore so because they're not getting the oxygen. That dark red mucus membrane now doesn't look as dark red as we kind of expect it to when we think about it. And sometimes it just is a slightly darker pink than than you would normally expect in that patient.
So just kind of take that with a kind of pinch of salt and for that for that kind of parameter. So what are our diagnostics that we can do for our patients? Often these patients, which we're probably gonna be running everything because what we're trying to do with these patients that we think that either have had an infectious insult or a traumatic insult is to kind of get to the bottom of Does this patient have a blood loss?
Do we have an infection? So again, we're thinking about our complete blood count. So think about, what our underlying disease is gonna show whether our patient is dehydrated as well.
And thinking about not just the the figures that we're getting on our complete blood count, but also using things like our dot plot to kind of assess whether we need to do things like, blood smear. So, for example, in this picture, you can see the Purple Line is a very hard, line. And then there's a you know, Then there's the blue, and this is kind of a shock in appearance, and I'll show you on the next side as well.
And what often this means is that this very sharp, shock thin line on these dot plots is that, that that now the neutrophils are actually being read as lymphocytes, and that's often a case when we have an increase in banned neutrophils. And so, again, thinking about our, blood smears thinking about doing, Salino gluten in patients, and making sure that we are looking for things like tox, toxic neutrophils, B, neutrophils, and and looking at platelets as well. So again, we know that there's that platelet activation.
Do we have an increased platelets in our in our fields? Do we have less platelets. And again have we Have we gone past that point of using a polar platelets?
And now, you know, now, now our patient is going into the high poke, coagulable stage. Think about serum biochemistry. So again, we know in especially in the septic shock patients that these patients have that loss of protein because of those leaky vessels.
So we might have had that hypoalbuminemia, we might have hypo bin, bin rub anaemia, and kind of more importantly, with these patients, I, especially when we're thinking about our fluid choices, is thinking about our blood gas analysis, so that might show us our lactate. So often these patients have this hyper because again, with our shock patients or with our patients that don't have good circulation, they start to go into the anaerobic met, metabolism. And we might have ionised hypocalcemia again, within, our kind of septic pathway.
A lot of calcium is used up in that process. And as a result of that hypert and often organ damage, for example, we might have increased, renal parameters as a result of prerenal azotemia we start to see things like metabolic acidosis in these patients. And so a lot of our focus when we think about our goals are active therapy is to try and reduce or eliminate that metabolic acidosis that might, be detrimental to our patients.
Your analysis is again, goes hand in hand with kind of kind of doing like that septic hunt of trying to figure out where that infection might be coming from. Especially if you've seen, that neutrophilia on, on your complete blood count. So think about where our patients are.
They often have, iso thin urea. They might have protein in the urine. Glucose and, again pyuria hematuria looking for things like cast that might kind of point us towards a urinary tract infection.
I'm again thinking about those patients that are showing science signs of coagulation and deficits or problems. As I said, they initially can be hypercoagulable. And then later, they kind of become hyper.
So you get an increase in either one or both your prothrombin or your, activated prothrombin times the a P TT. So as you can see here on the, on this one. Both the PT and the A P TT are increased.
In this instance, and so we're gonna again think about that when then, when it ties into our fluid choices when we're monitoring our patients thinking about whether we're watching for, our sis, and thinking about where you know how we give him fluid therapy. If his patient has, you know, increased clotting times, other things that we can do, to kind of do that septic hunt is to look at ar thoracic and abdominal radiography and ultrasonography. So again, we're gonna be trying to be detected in our underlying infectious or inflammatory disease process.
And that looking for secondary organ damage or free fluid. And again just remembering that we try and get cytology where we can, so we can send a culture and sensitivity. So just a kind of another example, of some diagnostics.
So again, looking at our, C reactive protein, our CRP is really useful, and we'll talk about that in terms of biomarkers in a second. But again, on this one, you can see the, on our dot plot on our haematology and that we have a solid purple, which then has that solid line into the blue and actually what you can see, which, kind of coordinates with what it says on the, on the chart is that our neutrals are high, but again, this is kind of being read as lymphocytes, on our dark plot again, blood acid is really useful, and good as a monitoring tool to see, progression of disease. I've kind of mentioned biomarkers as we've gone through, and there's as there's no kind of ideal or clinical gold standard for the diagnosis of sepsis, particularly in veterinary medicine.
And that's kind of because microbiology isn't always sensitive enough. And lab tests aren't always. They're kind of unspecific for use as a reference standard.
And because the septic response is so complex, there are, so there's, you know, a whole host of biomarkers that can kind of help us to accurately diagnose sepsis and monitor critically ill patients. But the problem with a lot of these for us in veterinary medicine, anyway, is that we would have to send off to a lab. And by the time we get those results back from the lab, those critically ill patients are either dead or we've treated them, and they're getting better.
So, we as a as a profession. Currently, we kind of monitor septic patients. And traditionally, and we achieve, you know, monitoring and and diagnosing them, you know, using biomarkers by measuring physiologic parameters.
And we've started to kind of use, our CRP, as a screening tool or again when we use CRP. It's great for, measuring response to treatment. So is it coming down?
I'm and kind of unofficially, It's not on this chart, but we kind of use lactate as a kind of one of our bio markers as well. So proc calcitonin, this PC T, is most commonly used in humans and again really available to them. But so proc proc calcitonin is, 100 and 16 amino acid peptide.
And it's a precursor for that hormone calcitonin. And so normally synthesis in humans, is in the C cells of the thyroid, and that kind of regulates the endocrine system. And So, proc calcitonin is converted to calcitonin and stored in those endocrine, Granules, and it's only released under sort of certain stress.
So when there's a lot of increased magnesium, and then so, for example, with septic patients, and so proton in, MRN a is expressed in many tissues. And that's in like the lung, the liver, kidney adrenals, colons, leucocytes. But in so in humans as Procar toin levels to kind of accurately differentiate sepsis from non infectious inflammation and that has been demonstrated to them to be the best biomarker for different differentiating patients with sepsis from those with systemic inflammatory, kind of reactions, which aren't related to infectious pores so great for them.
Love that for them. But, unfortunately, we don't have the ability to do that, at least not quickly. And so kind of what we can utilise from this table is that for the screening and infection diagnosis, we can kind of rely a little bit on CRP.
And we can look at our response evaluation, from CRP. And the issue is, and then you can see on this one. So the levels are not 10.
And I think once you get past past 100 on your, serum biochemistry, it doesn't read it anymore. So I'm not a very, sensitive or specific tool. But a tool nonetheless available to us, to kind of look at, maybe some severity.
But again, what we mainly use it for is to look at the, kind of response evaluation, to our to our screening of our of patients with sepsis. So the canine C reactive protein. So here's a nice little handy table.
There's no evidence of systemic inflammatory react inflammation. If you're like 0. 0.5 to 11 to 3 is kind of potential for resolving inflammatory disease.
Early mild inflammatory disease. You might start to monitor these patients more closely, especially if they're fitting in with those SARS criteria. And also a reason for an infectious insult or a traumatic, insult anything over 10.
I'm sorry. This is meant to say 10, is that you have a likelihood of systemic inflammation. And what happens is we get this degree of increase related to the variety of the inflammatory disease So, as I said, on our unfortunately on our serum biochemistry, it does only go up to 100.
But nonetheless, you can use it as a, a kind of monitoring tool, to monitor progression. The association of lactate level with mortality in patient and patients with suspected infection and sepsis, is kind of well known, well established. And it is part of the, surviving sepsis guidelines that committee their one hour sepsis bundle.
For those with sepsis, So, within their bundles. So they have sepsis six, and sepsis, three definition. What they look for?
It is this as a biomarker, basically, and then also as a monitoring tool. So, if you have an elevated lactate, within that sepsis three that first three hours of presenting, they kind of classify that into septic shock. So serum lactate is an important biomarker of tissue hypoxia and dysfunction.
But it isn't, unfortunately, a direct measure of tissue perfusion, but we know that we can use our tools like blood pressure monitoring to kind of work hand in hand with those two. So those recent definitions of septic shock. They also include, increases in lactate as evidence of that cellular stress.
To kind of accompany that refractory hypertension. And so the guidelines for humans are suggested that we use lactate levels, as a target of resuscitation, in the early phase of sepsis and septic shock, and in some studies, there was a kind of a relation from early goal directed therapy. And there was also a meta analysis of multiple studies that looked at targeting, reductions in serum lactate versus the standard care.
And they kind of recognise that, normal serum lactates aren't always achievable in our patients and septic shots, but from these, studies, they kind of figured out that those, it does support resuscitative strategies and also looking at that trending downwards. And that's what we're looking for. Rather than going from a lactate of 11 to a lactate of less than 2.5.
What they want to see is that our our patients are, resuscitative, resuscitative, responsive. And therefore that the lactate is starting to trend downwards. And so just kind of using it in that clinical context and also looking at our patients looking at blood pressure and things like that and and using it as a as a holistic tool.
So again, that's septic. Sepsis. Six.
Within the first six hours, they aim to reduce the lactate by 10%. So that's not a huge amount. Especially, when you think about some lactates, we get a bit itchy about them.
You know, you get a lactate 15. in previous years, we will be trying to really push that lactate down. But what you know humans are seeing is trying to just reduce it by 10% within the first six hours.
And that is gonna show us that our patient is actually responsive to those resuscitative, strategies. So I just mentioned kind of the surviving sepsis campaign. And those sepsis six and sepsis three.
And what these are is that this evidence based medicine, it kind of supports the implementation of treatment care bundles. And this concept, this bundle of care of, kind of refers to a group of therapies that when they're together that, they produce better results than if they're just initiated alone. So kind of recognising those SS parameters.
Looking at your biomarkers and your diagnostics and recognising that your patient has, an infectious insult or traumatic insult that, coupled with that systemic inflammatory response syndrome, is potentially giving your patient a dysregulated host response. Rather than just saying, OK, we're just gonna give some fluids. Those alone are not gonna work.
Versus when we implement our bundle of care together. And so, it increases patient, outcomes decreases that morbidity mortality, and it helps to also prioritise and standardise treat sepsis treatment protocols. And this actually this, photo was taken from an article, in the veterinary nurse by Catherine Grey.
And she kind of developed this kind of sepsis care bundle. And this is one that they just created, when she was working at the Royal Veterinary College. But it's, you know, I think it's something that is a great thing to do as a quality improvement and clinical governance within your practise.
So we've just created out of our own, And at the end, I'll show you kind of, advancements again for for our monitoring tools within the veterinary Looking at our veterinary early warning score system, is that you can do that together? You can look at your sepsis guidelines. You can look at these sepsis care bundles.
So sepsis six, was created, to prompt those medical professionals in in human medicine to start that within six hours of from admission to hospital. So again, for example, another thing that you can do with a new clinic is clinically order. And look at when antibiotics And, you know, think when bundles of care were implemented in your practise, from following on from when that patient was admitted, and that will kind of give you an insight to whether you need to standardise this little bit more officially.
Create protocols, create bundles on your practise management system so that when you, implement a sepsis bundle, it automatically prices the things that need to be. You know, it kind of a trigger for those people, that are implementing those protocols that they know what? Comes with those and again having, having laminated sheets in your hospital of those bundles.
So, for this one you can see for the sepsis bundle. For their IC U. They looked at the first criteria as well as the sepsis criteria.
So do they have a possible side of an infection? So think about intravenous catheters, arterial catheters. Chest drains, any in welling devices, surgical wounds?
so this was specifically for patients that were within the IC U that might move on to septic, processes. And so this isn't a super comprehensive list, but that might differ. Based on your practise.
So again, this was specifically for the IC U, and so you might broaden that out to the patients that you see, the you know, one of the the patients that you more commonly see and add them into this possible, infection, infectious processes, and again, So it kind of has a It goes back, and it says OK, no, you don't have any, cause for infections. OK, keep monitoring your S criteria until you potentially have this sepsis criteria. Yes.
If you do have this sepsis criteria, you move on to this next one. And do you have any of these as well? So Do you have a lactate over to, millimoles per litre.
Do you have a, a decreased, systolic blood pressure, or it increases the blood pressure. Changes to glucose increases. Renal liver, values.
We know that our lactate often will trend upwards. Our glucose will trend downwards because bacteria love to eat glucose. And they poop out the lactate.
Is how I like to think about it. And again, So thinking about our urine output as well. So thinking about, whether we have any, signs of that multiple organ, dysfunction as well.
So again, their bundles then move down to severe sepsis and sepsis. That includes things like I'm starting therapy. Start intravenous therapy.
Intravenous fluid therapy, monitoring our ins and outs. Oxygen delivery is very important again. These patients are gonna be hypoxic, potentially hypoxemic, depending on if they have things like, pulmonary thromboembolism as well.
So so the sepsis six, is the one that's most commonly used. And they start treatment within six hours of admission to hospital. And that includes administering high fluor rate oxygen, taking blood cultures, administering broad spectrum antibiotics, administering intravenous fluid therapy, measuring the serum, lactic levels and haemoglobin.
And looking at that urine output more accurately as well. To develop on from that, they then went to, kind of a sepsis three, which looks within taking action within three hours for those with organ failure. So again, recognising those biomarkers for organ failure, and using things like that.
So, for scoring, sequential organ failure assessment, scoring system. In human medicine, they use this to kind of recognise or organ failure, and they implement sepsis three. And then they follow that by completing the se sepsis six hour bundle.
So the three hour is within that six hour. And that's the most up to date kind of bundle. By the Euro European Society of Intensive Care, Medicine and Society of Critical Care Medicine.
And then within that they looked at this, So first, this sequential organ, failure assessment. And that kind of also developed to, replace CS in the human field. And so they kind of assess them on that.
But unfortunately, it's not always, as simple for our patients. So we still kind of use. We use an indication of the CS, as a good marker for highlighting this particularly and, well, our animals again, just remembering that a lot of our patients in hospital that it will probably meet the CS criteria.
Early goal directed therapy kind of goes hand in hand with these treatment care bundles and again will potentially influence you when you come to look at doing, you know, making your own protocols and practise. But basically, it just means that a technique that's used in critical care medicine involves intense monitoring and aggressive management of perioperative hemodynamic pa in patients with a high risk of morbidity and mortality. And so the aim really, that came about from go active therapy to ensure adequate tissue oxygenation and survival.
And this kind of came about I was kind of posed in 2001, and it's really useful in terms of when we think about what are we hoping to achieve by implementing the bundles? There was a meta analysis in the I'm New England Journal human. I'm medicine.
Which kind of I'm I it I didn't Didn't the evidence didn't really support early girl directed therapy. Especially when it came to, thinking about it in terms of sepsis. And so I'm not gonna go into too much about I, like, focus on it too much.
But what I want to say is that actually really think about, kind of the parameters that we're gonna monitor. And what our specified targets are for these. So these are, like, the early goal directed therapy.
end points for the first six hours for, our patients that, is set out by this early goal directive therapy kind of, directive. So, for example, we don't really do central veins pressure anymore. You need a jugular catheter if you've got coagulation.
problems. Then that's not appropriate. And it's kind of outdated, so we can use noninvasive blood pressure, and that's just fine.
So using that marine arterial pressure, and again, thinking about the sepsis Three, again, that was creative human to take, with again with a pinch of salt, but kind of pair it with this early girl direct therapy to think about OK, what do I want my immuno blood pressure to be as a minimum. What is my urine output? What is my hopes for my urine output gonna be?
And when I look at my mixed venous oxygen saturation again, we could do this in our blood gases from a venous sample. We don't have to take arterial samples, which, obviously we know is increased risk of bleeding to these patients. A high skill level, is painful for these patients.
And so Venus is just fine. And again things about he, hematocrit as well. So what are our goals?
In veterinary medicine. So obviously we want our heart rate to be kind of in that normal range again. Respiratory rate pulses to be we wanna be able to palpate our femoral and dorsal pedal arteries.
Thinking about our systolic and our mean and blood pressure. So we want it above, 60. Hopefully, we want it above 17.
So between 7080 is a minimum. We do. Ideally, we want our lactate to come down, and be less than two mills per litre.
But again, thinking about that 10% reduction in the first six hours. Urine output, I think about over 0.5 to one mil per kilo per hour and making sure our patients are responsive.
So this kind of goes hand in hand with when we're given, like our, our fluid therapy. Because again, that early goal direct therapy kind of just looks at the hemodynamic status of our patient rather than looking at everything in our patients. So when we think about our hemodynamic goals, this is what we want to see.
From our early goal directed therapy. So one of our, treatment, that should be in our bundles is that we know that this is fluid balance. So thinking about whether our patients have shock dehydration, how are we gonna replace that?
Do we need to give small a bo Bo, to see if our patients are, fluid, responsive? And we're gonna know this by, you know, looking at these previous parameters is my like, you know, my men to your blood pressure. I'm now moving up from 50 to 60.
If it's not and I've given a flu bolus, I might try another flu bolus for my heart it's coming down. But now if it if on my second bow list I'm not seeing a change in my immune orter blood pressure, my heart rate's not really changed. My patient isn't fluid responsive.
And therefore, it's not appropriate to keep drowning this patient employ, because that's essentially what we're gonna do. So we want this hemodynamic stability. So, cent means pressure of 8 to 12.
centimetres of water or immunal pressure of over 70 millimetres of mercury And this increased urine output, you know above, or equal to 0.5 mils per kilo per hour. But if they're not adequate in responding to that fluid therapy what?
Where is that fluid going? So again, thinking about our, our point of carriage sound, Seeing whether our patient has third spacing whether they have, free abdominal fluid. Pleural fusion, pulmonary edoema.
Do they have peripheral edoema? Can we look at things like our, called of vena cava to look for our volume status as well? And so when we've done that and and we're kind of seeing that our patient potentially has this form of distributive shock.
So this septic shock, I now we're thinking, OK, well, fluid therapy. Our fluid is going into the vessels and immediately being leaked out. Our glycolic is damaged.
We're not holding proteins, and we're just gonna continue to lose that fluid, and that's gonna be detrimental to our patients. So thinking about our vasopressive. So these are used to increase our blood pressure.
So we might use, norepinephrine You may use, epinephrine. So noradrenaline, or adrenaline as CRIS. Because it's gonna cause that peripheral vasal constriction with our, adrenaline.
We're potentially gonna cause increased, pro tropy as well. So no adrenaline is preferred. Vasopressin is another one that just again causes that peripheral vasal constriction.
But it's very expensive, so we're probably not gonna, under vasopressin. But our vasopressor nor noradrenaline is perfectly fine. We might, administer inotropes so positive inotropes like our, things like that.
Medin, to increase, the heart contractility as well. To, help with that fluid balance. And so hyperperfusion and sepsis.
Due to hypothalamic or peripheral Vasil nation or myocardial depression can be quite detrimental to our patients. So that no adrenaline, is kind of the first, choice. And it's a potent alpha one and beta one, Adreno receptor agonist.
And that gets that peripheral based constriction increased me not pressure. And it has a minimal effect on that heart rate as well. So we kind of start and we titrate from nt 0.1 mcg per kilo per minute.
Up to about naught 0.4 mcg per kilo per minute. We wanna target again.
So we're thinking about our target. So both, immuno pressure of 65 millimetres Mercury as a minimum. And and so now we're talking about our fluid therapy and what we're gonna use so often we use, our crystalloids, but remembering again that these are quickly excreted.
If we have Hypo album, they're not gonna stay in our intravascular system very long. And so I'm again thinking about your electrolytes. Do you have any electrolyte imbalances?
Do you have a metabolic acidosis? Therefore, metabolic acidosis, sodium chloride 0. 0.9% is not, the correct choice, because that is an acidic fluid, and we don't want to further acidify our patients.
So thinking about our losses as well. So if we've had again this distributive shock, we've lost lots of proteins. And we have this hyper anaemia with low total proteins and our patients or we've had a blood loss from a trauma.
Do we need to give things like fresh, frozen plasma, or pack for blood cells again, If we know that we've got, coagulation deficits, we've got that increased PT or a P TT. Do we need to give things like fresh frozen plasma or frozen plasma or even for precipitate, to our patients to kind of help them with those two factors? So again, this is kind of where we kind of start to have some differences with the, between the human surviving sepsis lines and hopefully, what will be the veterinary surviving sepsis guidelines?
In the future, is that they they recommend at least 30 mils per kilo, of IV preso within the first three hours of resuscitation. And that's not always appropriate in our patients. For various reasons, they might have a, you know, a cardiogenic failure, and they might have renal failure.
They might be very small patients, and 30 mil per kilo is a large amount. So we know that our shock shock bows are like 70 to 90 mils per kilo in dogs and 6045 to 60 million kg for cats. Kind of like, you know, 30 mil of that is it is quite a large amount for cats.
That's almost half of their, blood volume that we're adding. And especially if we've got this non responsive, fluids, this non this, this non fluid, responsive kind of shock or, patient that if we dump 30 mils per kilo, onto a cat, for example, that's a large amount now, and the patient is gonna be kind of really fluid overloaded, which we are gonna be concerned about Oxygenation. I kind of mentioned it in those treatment bundles is actually really important.
So this distributive shock, especially, is gonna affect that fusion and the oxygenation. Our patients are gonna be hypoxic. They're also gonna have this dyslexia.
So this cellular, oxygen consumption, we we might have a a potentially increase and pack cell volume from either from blood loss from whatever's going on, or, you know, if you've got coagulation deficits and we're now kind of, hypercoagulable and kind of bleeding out, And this disseminated in scul coagulation is that now, we have less oxygen carrying capacity. And in these patients, they need oxygen. And whether that's, you have them in an oxygen tent or you are placing nasal oxygen catheters, nasal oxygen problems, high flow oxygen.
If you have that, that that is actually great. And Tole tolerated well in these patients, or in some cases, it might be actually indicated to put these patients on a mechanical ventilator. And again using our point of care ultrasound as, like, a monitoring tool, to see whether these patients progressing again, looking for things like glide signs and to make sure the pleura are rubbing up against each other and looking for things like our artefacts, like bee lines.
I'm looking for free fluids that can be sampled, or removed If that's causing, pro, you know, further detriment to our, respiratory system sepsis and produces a hypermetabolic state. And that really requires the support with adequate nutrition and gastrointestinal support and, so so fluid therapy and oxygenation and antibiotics are kind of the cornerstones of, septic treatment. But if this is actually just as important, and, kind of the gut has been identified as kind of a key organ in, sepsis.
And often what we see is this, gastrointestinal dysfunction that's really common. So early. Nutritional support is primarily used to maintain integrity.
Doesn't test on mucosal barriers to decrease the chance of bacterial translocation. And what we want to, you know, hopefully do is give nutrition. So as a result of this fibro metabolic state, often we get these, complications.
We get GR. I ulceration. And so we might use things like our, history to antagonist on protein pump inhibitors like meprazole and to reduce that risk of ulceration.
And so we've got a lot of regurg regurgitation. If there's evidence of, gastrointestinal haemorrhage again thinking about using a point of care ultrasound or sending these patients for, a full, ultrasound, diagnostic kind of image. And then we might think about things like sulphate.
We can give this again by, our feeding tubes. If our patients are undergoing abdominal surgery because the the underlying problems are often you know, most commonly we see these septic abdomens, from things like perforated foreign bodies. And then we might just consider to place those esophageal gastrectomy tubes or and feed and choose when we do that.
So, if, enteral feeding isn't tolerated, and the partial parenteral nutrition can provide that nutritional support while we get that, you know, the internal nutrition kind of reinstitute, reinstated. And we just kinda wanna prevent any further ulceration or treat, gastrointestinal bleeding or ileus and really help to keep the guts kind of healthy. As possible.
So, place of feeding tubes, again kind of ties in, to these patients in terms of our holistic care. So thinking about the Kirby's rule of 20 nutrition. So, offering different foods, having owner visits to try and see if they'll get to eat.
But when they're really sick, that naso gastric tube especially might, help with gastric il. We can syphon off, material. We can feed, through that tube.
We can give medication through that tube. We can count that towards our fluid balance as well, which is really important to patients that might, become, you know, these patients can become very quickly fluid overloaded, and again, just bonding time with these patients. From a nurse perspective, sitting and doing feeding tubes gives you the opportunity to do, other things like that TLC, you know, washing their faces, giving them a broom.
Doing physical therapy whilst you're feeding these patients as well. And again when we know that in these patients we often get this hypo glycemic, response from this type of metabolic state, we can provide nutrition, which is gonna, increase our glucose rather than having to supplement that intravenously. Which can cause, you know, large increase or, phlebitis.
And obviously, phlebitis is a risk factor for sepsis. So, particularly when we have this pro and anti inflammatory response. What we see is, as well as our systemic inflammatory response.
And we get this causes, and and so that's pro. Systemic inflammatory responses is pro inflammatory. And we get what we get is this anti-inflammatory response which normally balances on a scale.
But what happens is that kind of over overcompensates, and almost these patients become, immunosuppressed at this point. And so, anything can cause an infection and make and, you know, progressively make that worse. For that patient, obviously, antibiosis is kind of our main, part of the treatment bundle and mortality significantly increases for every hour of delay.
For that antibiotic therapy, so particularly if we can, I I identify the micro organism source. And then, realistically, we want to try and, get samples as aseptically as possible, to submit the sort of culture and sensitivity. And so our kind of goals is, what we want is this an intravenous empirical antimicrobial therapy, and that's directed to all potential infection, infections and sources.
And that should be given as soon as possible. So we could broad spectrum first as quickly as possible. Hopefully, once we get that, kind of, culture and sensitivity back, we can, narrow our coverage down.
So initially, that coverage should cover, Staphylococcus and streptococcus and E coli. And any infectious process that can, and sh you know, can be surgically drained or debrided should be treated as promptly as possible. And although, yes, we have this antimicrobial stewardship, within human and veterinary medicine.
With sepsis, the quicker that we, implement our antivirus is the better outcomes for our patients. And we can always discontinue, for for these patients quite quickly. So reverse bar nursing is, obviously another.
Another caveat for these is, we should be wearing sterile gloves when we're handling in dwelling, catheters, urinary catheters, chest strings and central lines. We should be at least doing good hand hygiene and wearing gloves with these patients and and gowns. So that we're not, we're we're we're decreasing the risk of hospital acquired infections as well.
So in the human Sep, sepsis guidelines. They kind of, they suggest two antimicrobials with gramme negative coverage. For empirical treatment over the, you know, versus one gramme negative.
Agent. That's kind of a weak kind of recommendation from the thing. But they also again use like proton as a biomarker to start antibiotics.
So they have that. Another tool that helps them. So, for as in fact, medicine, just starting the antibiotics as as possible.
We can always just continue if ne, if if necessary. But I'm again starting with at least one. I'm running negative coverage.
I'm potentially two depending on, you know, clinically what a patient is looking like. And again, I'm kind of out there, but not necessarily. Strong evidence base is to give, increased, a decreased time between, our intravenous antibiotics that we're not hitting that we are and kind of, you know, human medicine.
They actually put them on CRIS of, of their gramme, negative. And agents. We're not able to do that, obviously, with calm oxy cloth.
But what we can do is increase, decrease the time between those doses. So rather than being an a power dose, we're reducing it to about, 4 to 6 hours, to to increase, you know, to to prevent that drop in coverage. So, as I said, these treatment bundles and early goal directed therapy together.
And what we hope to achieve within at least the first six hours, but hopefully within the first hour of recognising and picking up on the third criteria and septic criteria. Is there a measuring serum lacto looking for that 10% decrease, obtaining cultures before antibiotic administration. We're not always gonna do blood cultures, but potentially we're doing swabs or, fluid collection starting a broad spectrum antibiotic within the first hour.
Treating any hypertension or elevated lactated fluids Or potentially, administering invasive presses for any hypertension that's not fluid. Responsive. And so after a couple of, or small boluses, if they're not responding to that kind of implementing that invasive press therapy, and again, we're not potentially gonna look at this, central venous pressure.
But we might look at is our, mixed venous, oxygen saturation, of at least above 65%. So just quickly this. So for this, sequential organ failures, assessment.
It's one of the most commonly, organ dysfunction scoring system that they have, that they use to critically assess critically ill patients. But it doesn't include things like, fibrinogen or other markers of fibrinolysis. So there's degradation products.
But what it does look at is the activation of coagulations from cytopenia Looks at organ dysfunction. So lungs, so looking at hypoxemia based on partial pressures of oxygen, oxygen saturation, fraction of inspired oxygen, they look at the brain and again another, organ disorder. So you can look at the Glasgow Chromos score, and for us, that would be a modified Glasgow chromosome.
I am liver looking at the total bilirubin concentration. I'm looking for things like the heart. So thinking of hypertension, and also looking at heart rates.
And again, the kidneys are high creatinine concentration is urine up, but, and so they kind of measure measure the social score admission and then sequentially, through their progression, or looking at the initiation of organ injury, and so they kind of use these variables to predict death or prolonged IC U stay in patients. And again, just kind of, it we have kind of looked at the use of, sofa scoring in our veterinary patients. This first study, is about 35 dogs.
And it did show some discrimination between septic and non septic patients, but unfortunately, not enough kind of. It's not a big enough sample size, to kind of confirm that and then studying them to the same one that was in the Js a was 45 dogs for sepsis or so. So again, I'm kind of a small cohort.
And also a retrospective study, but looked at I'm it just doesn't Basically, the conclusions of this study was they didn't have a great specificity or sensitivity. And so it shouldn't be used as a rapid F alone. So we you know, we know that we're not always going to fit into the human human box.
And the same with that serve. We know again, it's not It's not super sensitive or speci, specific, and again shouldn't be used as a rapid tool on to diagnose sepsis. But what we can do is use it with these other tools, like our lactate RCRP.
We might use a sequential organ failure assessment as well with, those to kind of look at our patients and how we're progressing through the disease stone and kind of more excitingly. More recently is that we have, what is called the veterinary Early warning school? And I think more is to come on this, and that's very exciting.
Is looking at these, kind of similar to both S es and kind of, so in the NHS as well, they have news. So, it's modified early warning for, and news. And again, they're very similar to the sofa sporing in that they kind of put patients in for the, for example, this one.
Their views is that they put them in red, amber or green. So those in green, you might monitor once a day. Those in amber, you may mo monitor, more regularly.
If you have more amber and more red, you're gonna start to think about, Does my patient have a septic process? How can we, monitor these patients? Do we need to look at the lactate?
Do we need to start antibiosis? So again, this is something that we within our clinic. We had a journal club.
We looked at this. We looked at the sofa scoring. We looked at, Catherine Gray's treatment bundles as well as the human, bundles.
And I'm more than happy to share, via email if anybody wants to see them. Kind of just kind of the treatment bundles and guidelines that we came up with that for our practise. And it might be slightly different for every practise.
But what we're hoping to do is kind of, create a a solid SOP that, is initiated whenever you know. So, for example, if we have, a red score of over over two, and then it triggers to go down into the our septic. So, back to kind of Catherine's, treatment bundles is the, Is there a septic criteria that is met?
So ours is slightly bigger than this. And we've also amalgamated, the view scoring just to be on a one sheet page. So we have views on one side or modified views for our practise, and then and on the back of that is kind of that setting criteria, and then that triggers.
Those treatment bundles. So again on our practise management system, our plan is to, have a bundle that you click on and it immediately, we will kind of have those prompters. So, fluid therapy, antibiosis oxygen therapy.
I kind of priced within that bundle. So that, whoever's whoever's implemented that knows, exactly what what they need to implement. And so that is kind of a whirlwind tour of the septic patient.
And how we can monitor our patients what we're kind of looking for in our patients and how we're treating them. But if you have any questions, please feel free to email. I'm always happy to answer or have a discussion.
Or again, if you want to look at my pro protocols that we did, and within our practise, I'm more than happy, to kind of share some of those. So thank you very much.