Thanks very much, Bruce. So tonight we're gonna be talking about the approach and stabilisation of the septic patient. So as with all of my, webinars and lectures that I like to do on patients, I like to go through the path of physiology and really sort of get a greater understanding of what's going on with our patient before we start to talk about.

Diagnostics and treatments, and our monitoring techniques. So what is sepsis? It's defined within the, surviving sepsis, sepsis guidelines as a dysregulation, so pro and anti-inflammatory response to infection and trauma.

So, It's a progressive disease process that can cause multiple derangements, and this can involve several different organs and systems, as well as a critical reduction in tissue perfusion. So it's Considered a potentially life-threatening condition, and it simplified its body's response to an infection. But we really want to, remember that this is just regulated is the key phrase, because the body will always have some sort of inflammatory response, in response to, you know, infection and trauma, but within sepsis, there's an inappropriate, response as well as it not being regulated.

So from this, the body normally releases chemicals into a bloodstream to fight an infection. So, sepsis occurs when the body's response to these chemicals is out of balance, so it's regulated, and it triggers changes that can damage multiple organ systems. And, sepsis and septic shock, a major causes for morbidity and mortality in both human and veterinary medicine.

We can get systemic inflammatory response syndrome, prior to sepsis, and this describes a clinical condition characterised by widespread activation of the inflammatory system, secondary to sterile inflammatory disease or infectious insult. So in both SES and sepsis, there's going to be a disruption of homeostasis, and we'll go on to talk about what this means for our patients. So a normal pathogen, a normal inflammatory response pathogenesis is that there's an insult that then triggers a local activation and a complement.

So we get this activation of macrophages, and release of tumour necrosis factor alpha and interleukin one. Which then causes the recruitment of neutrophils, and release of oxidants and proteases, and ultimate will lead to the injury of cellular and matrix elements. So when we have an inflammatory response that's triggered by an insult such as trauma, uncontrolled infection, anaphylaxis, and these are all things that can cause sepsis, we have these pathogen associated molecular patterns of pumps, and damage associated molecular patterns, so damps, these set off chains of events and through the sensors and affect the cells.

These then trigger complex protein systems, so things like coagulation, as well as lymphatic cells to release mediators and biomarkers, such as interleukin one, and the tumour necros, yeah, tumour necrosis factor alpha. And in turn, these can then create these cytokine storms that we hear about, which will impact on organ function. So This is going to cause your typical sepsis sign, so your shock, respiratory distress, edoema, your leaky and gastrointestinal system, you get this vomiting diarrhoea as well, you know, hyperthermia, and, .

Other things that indicate certain sepsis might be a cardiac disease as well. So for the inflammatory response, we get this acute inflammatory response that causes a cascade of both pro-inflammatory and anti-inflammatory mediators. And so again, remembering that with sepsis, we have a dysregulation of both of these mediators.

There's a vital response to injury, infection, trauma, and many other insults, and the inflammatory response must be triggered to bring about a recruitment of these blood leukocytes, and activations of tissue macrophages, and the production of a series of mediators. All immune responses are going to start locally, responding to the pathogens on a local level, but ultimately will become systemic. And this is true for any, you know, inflammatory response.

However, the difference between it not becoming sepsis and sepsis, is that there's not enough time, if the, if the local reaction and the local pathogens then go to systemic. So around the body and the body hasn't had a chance to build up the . Correct mediators and to stop those pathogens.

That's when we start to get sepsis as an overload of these pathogens systemically. So in sepsis, there's an often an unregulated production of low pro-inflammatory mediators, that can cause organ multiple organ failure. In response to the presence of pathogens, monocytes, and macrophages, these are all produced through, they release cytokines, and these are the strong pro-inflammatory actions and assist the defence mechanism, so attracting these activate neutrophils.

In human medicine, they do have what is called a sofa score, so it's a sequential organ failure assessment, and they score 0 to 4, on respiratory coagulation, liver function, cardiovascular function, central nervous system, and renal. So they use things to measure, these, such as creatinine, bilirubin, mean arterial blood pressure. Glasgow Cromaco and platelets and function platelets and your PAO2 and FIO2 ratio.

So we'll come to you later when we talk about, our biomarkers and our goal, goal directed therapy, treatment. In that, these are actually, although they're for, human medicine and they're more for multiple organ failure, mods and monitoring, we can incorporate this into our sepsis monitoring. So sepsis causes a disruption of homeostasis, and this is through a non-controlled cascade of inflammation.

And so it is excessive coagulation with impaired fibrinolysis, and this then contributes further to the inflammatory condition, as well as causing this microvascular hypo hypo perfusion. Organ dysfunction and high mortality. So it's common with septic patients that we get, they get thrombus, as well as, they do then start to go towards disseminated intravascular cardioopathy.

And just circling back to these pathogens, the cells of the immune system sort of express a pattern recognition, pattern recognition receptors, the PRRs, and that detect danger via these pumps that I mentioned, a couple of slides ago. And these, respond with a specific immune response. So they go initially through these toll-like receptors, and these pathogens, and they lead to these pumps, which then, Along with these pattern recognition receptors will create a a specific response to that pathogen.

And when we're talking about the homeostasis, of sepsis and so and septic shock, they have two phases, so hyperinflammatory, and hyperinflammatory, and therefore, the monitoring the biomarkers, is going to change over time because we're gonna have changes to this homeostasis, and how the body responds to this. So with the hyperinflammatory phase, we have a low risk for secondary infection, whereas with hyperinflammatory towards the end of the, They, their sepsis or further into the sepsis, they have a high risk of infection, secondary infection, as well as high risk for immunosuppression and immune dysfunction. So let's kind of review the path of physiology, and what we've already been through.

So the inflammatory response may start initially locally, but if it's severe, it's going to cause systemic signs because, the body hasn't had a chance to block those pathogens from, infiltrating systemically. And so this would mediates information into the circulatory system and instigate this global activation of the inflammatory system. So we get this systemic full body inflammatory response to what might be might be a local inflammatory response initially.

During gram-negative sepsis, the lipid a portion of lipopolysaccharoids, and the glycolipid component of the cell wall will bind this, Lipopolysaccharide binding protein. The initiation of intracellular signalling and will then begin a transcription of inflammatory cytokines. So from this response, and we also get a generation of anti-inflammatory cytokines, soluble receptors and receptor antagonists for cytokines.

So when we get this, we get what is called the cytokine storm. And this is when the immune system is fighting pathogens or repairing this damaged tissue. We get these pro-inflammatory cytokines signalling immune cells such as T cells and macrophages to travel to the site of infection, so it's causing everything and the body has to this site of infection, and it's disregulated and, you know, it's not an appropriate response to what might be going on.

And in addition to this, we get, cytokines activate these recruited immune cells to produce even more cytokines. So it's just a storm building and building and building. And this excessive production of pro-inflammatory cytokines can be very dangerous to our patients.

So here's a nice sort of diagram, but what we're really looking at when we're looking at sepsis and what we're the most concerned about our patients deteriorating is going to be from this cytokine storm. We have these local pathogens here, they go through the dumps and so there's damage associated media . Molecular patterns, and then, gram-negative, especially, endotoxins, we'll go through, what is known as a toll-like receptor 4, and this is the most important within sepsis of remembering, and since gram-negative bacteria, is going to pass through to these pathogen associated molecular patterns, these pans, where they're gonna, alongside the pathogen recognition receptor are gonna cause .

An immune mediated response. So again, our cytokines, we're gonna have, this storm, because they're just gonna. Produce more and more cytokines as well as pulling these neutrophils and monocytes to the area.

I'm So the systemic response is going to lead to this cascade where we have you know, our coagulation cascade is gonna be affected and, you know, there's gonna be dysregulation of microcirculation, as well as phagocytosis, excessive phagocytosis, and fibrin and depositions of fibrinolysis. You know, which can lead to a patient's clotting and appropriately, and can also lead to disseminated intravascular coagulopathy as well. Just a quick note on the gene transcription of inflammatory molecules.

So, these are on neutral extracellular traps, which in turn immobilise platelets and erythrocytes, and so these are another trigger for this DRC. And neutrals use these nets and to tell the pathogens, . Where they are, and, and the DNA coated, .

With proteins, and they send them into the vascular, vasculature and they cause endothelial damage. So this further triggered more so basically the patient's sepsis will get worse. So then we're looking at diagnostic criteria for our patients, and what this means for our patients is that we're gonna look at clinical manifestations, and how this relates to biomarkers, and, and what diagnostics we we be doing with our patients.

So I talked about that hyperinflammatory and hyperinflammatory phase. So in the early stages of septic shock, and you've got this hyperdynamic phase, these patients are going to potentially show dark red mucous membranes, you might get these brick red mucous membranes. With a short capillary full time, so less than 1 2nd.

It's important to remember as well with these dark red mucous membranes. Yes, that is the, what you would read in a book, and this, you know, this like the clinical mass manifestation, but think about these patients in terms of if they have underlying diseases, . You know, if they already have hypoxia, then these patients might be pale, and they might have a different colour mucous membrane and therefore, These patients still might have like a, a pink tinged mucous membrane, but if you were monitoring that patient earlier and they had pale mucous membranes, that can indicate this change, this hyper hyperdynamic phase.

So it's just important to remember that it's not always textbook and dark red mucous membranes. It can just be a slight change from what the patient was before, and just remembering those underlying conditions as well. So, elevated heart rate and respiratory rate, obviously this is in response, to this, hypovolemia that we get, .

We have got a reduced cardiac output, so our heart then starts to increase the heart rate and respiratory rate to try and get that oxygen pumping around as well. And fever, so hypothermia often leading into pyrexia, especially if it's an infection. As well as bounding pulses, and signs associated to this peripheral basodilation.

So if we've got ACGs, we might have, we might have arrhythmias, and we may have pulse deficits as well. And then in the more advanced stages, so when we're talking about this hypoinflammatory stage, these mucous membranes may seem grey and dry, with an increased capillary full time and these weak pulses. So just remembering that there's often two phases, when we're looking at these patients and, sepsis or septic shock.

I'm So, sepsis currently defined as a systemic inflammatory response to infection or dysregulation. And so what we need to think about with this dysregulation, . Response to infection, is to think about the dysfunction of all bodily systems, and when we're looking at the criteria, I'm remembering what the normal homeostasis is for, those, organs.

So systemic inflammatory response syndrome is a complicated syndrome that might occur as a result of infection, but it can also occur from trauma, burning lesions, Strokes, and many other aggressions such as anaphylaxis, . So, it's It really can happen with anything. We just have to be mindful, you know, it can happen with respiratory disease.

It's just the body's response to, this infection or to a, an insult. So currently SERS is defined as a condition in patients that show two or more of these criteria, or three or more in cats of the following criteria. So often it's good to remember this criteria because SERS and sepsis go hand in hand.

So a temperature over 39.7 degrees or less than 37.8 degrees.

A respiratory rate over 30 breaths per minute. A PACO2 of less than 32 millimetres of mercury. A heart rate of above 116 dogs or above 215 cats.

But again, with these remembering what breed you've got, as, as well, particularly in dogs, you know, if you've got a large dog, The ordinary, say, a Labrador might have a resting heart rate of, you know, maybe 60 to 70, and all of a sudden it's got a heart rate of 130, 140. Yes, it doesn't necessarily come into this diagnostic criteria as such, but if it meets, you know, two, if it meets another one of those criteria, maybe thinking and suspecting sepsis in these patients. And a white blood cell count of more than 19,000 or less than 4000, or, an increase of more than 10% on neutrophils.

So when we talk about biomarkers, and these are objectively measured, in response, and sensitivity and specificity, . I Must be considered within the biomarkers and so there's a classification. I'm, I've, I A few things that they will look at for biomarkers.

Within normal practise, it's very difficult to tick off all of these, and so I'll go through the ones that we, you know, going to be looking at within practise. But you can see how this diagnostic criteria that I've just listed now and fits into those hyper and hyperinflammatory phases of sepsis, and how that's the body responding to, that pathogenesis. So cytokine biomarkers such as interleukin one and tumour necrosis factor, and so interleukin one receptor antagonists, and that would be what we were looking for, cell markers.

Coagulation, so activated partial thromboplastin, time, this is, that's something that we can do in practise, because we talked about that coagulation cascade, is gonna be, Injured, and so we're going to get increases in our APTT. As well as things to look out for for biomarkers, vascular endothelial damage, and so platelet derived growth factor, basal dilation, so, angiotensin convert an enzyme, presence of that, organ dysfunction, . We can use troponin, so you may be able to use this in your practise, but you can measure troponin, and it's not necessarily, done very often in our septic patients because we often have all these diagnostic criteria and, our other biomarkers that we would, more heavily rely on.

We have acute phase protein, so calcitonin. Again, you could send that off to the lab, but by the time you get a result from that, your patient's probably going to be in severe sepsis. And metabolic.

So lactate is going to be this one thing that we really concentrate on, and measure that's an effective way to measure response to treatment. I'm using lactate, and then things like hao dilations and neuropeptides, again, not something that we're going to be commonly doing with practise. So when we're talking about being in practise, and looking at the diagnostics that we can do in our patients that we suspect have sepsis, septic shock, or a complete blood count.

So we're going to be looking for that, you know, either an increase or you know decrease in white blood cell count, or that more than 10% increase in that neutral, and neutral increase. Make sure that you're thinking about your underlying disease, whether it's concurrent with what's going on with them, you know, if you've got an inappropriate influx of white blood cells, and, your patient, you know, doesn't seem to have an infection. It's not coming in for an infection, so it's coming in for, you know, respiratory disease, .

You know, if you've got this all of a sudden you've got this high white blood cell count, that's, you know, that might point you towards sepsis. And obviously taken into fact and dehydration as well. Serum biochemical profile, so in particular hypoalbinemia, hyperbiliary ribinemia, .

We're going to be looking at our liver function in our patients and we talked about that sofa score. Bilirubin is a big thing for them to in human medicine that they assess the liver function, within, multiple organ dysfunction, syndrome and, sepsis. Blood gas analysis, .

So hypolactemia is gonna be often what we are getting in our patients, as well as ionised hypocalcemia. So if you've got, blood gases, and it's really good to do your ionised calcium. As well as often these patients we're gonna be getting a metabolic acidosis.

And this is often because of this hyperlactemia. So these are good, diagnostics to continue throughout your monitoring as well, especially blood gases, they're quite easy to do, and they're readily available near the patients. You don't have to be taking lots of blood as well, if you have the pre-loaded syringes.

Urinalysis, things that we're gonna be looking out for in our septic patients or eyeuria, proteinuria, glucoseura, pyurea, hematuria, casts, anything that might point towards, potentially, an infection, a urinary tract infection, that might be causing. The sepsis, . As well as looking at potentially whether our patients have a coagulation problem.

So if they've got hematura as well, this might be pointing towards, you know, our coagulation and cascades, these patients being hypercoagulable. So Apologies, there is a typo on this next bit, so coagulation test and perform, so initially hypercoagulable. Because we have a super analysis, and then later we have a hypocoagulable so we get an increase in, one or both the prothrombin or the APTG.

So this is probably one of our key things to keep monitoring and monitoring and doing a diagnostic in the first place when we suspect sepsis, because You know, a lot of the time, this coagulation cascade is going to be affected. As well as this, we got thoracic and abdominal radiography, and ultrasonography. So we can do cage so or you can do a full sonography but doing a flat scans, so assessing for fluid, free fluid, fluid-filled cavities, .

Are going to be helpful because we can do cytology and from that cytology, obviously we can get a lot of information. You know, we can send it off for culture, you know, if it's blood, we can, you know, we may potentially know that we've got a cavity bleed, and these are really these diagnostics, and diagnostics are aim for detecting these underlying infectious or inflammatory disease processes, as well as any potential potential secondary organ damage and free fluid. So early goal directed therapy, is a key word to run around in sepsis management, and both in human and veterinary medicine.

So Early goal directed therapy was first proposed in human medicine in 2001. And this quote is from Emmanuel Rivers, and this was in the New England Journal of Medicine in 2001. He said that technique used in critical care medicine involve an intensive monitoring and aggressive management of perioperative hemodynamics in patients with a high risk of morbidity and mortality.

So this basically I got early goal directed therapy, is an aggressive management that's got targets for your therapy and it's very quick, . And it's aimed to reduce this morbidity and mortality. And the aim of the goal direct therapy is to ensure that our patients have adequate tissue oxygenation and therefore, they'll hopefully survive.

So surviving sepsis guidelines work, with, what are called treatment bundles, and these have proven, really efficacious, in reducing mortality, in particular, lactate, . And What they suggest is a lactate bundle, a sample of cultures bundle, early antibiosis, hypertension treatment with IV fluids and vasopressors, target and central venous pressure and oxygen and so . That mixed venous oxygen saturation.

So when we look at our parameters that are going to be monitored intensively and managed aggressively to specified targets. So central venous pressure is falling out of favour a little bit just because we have to have jugular catheters in our patients to do this. We've got an increased risk of, Introduction of further infection and obviously with our patients that you know, potentially a hypercoagulable, .

They are gonna be at more risk of bleeding, you know, I'm bleeding out around that jugular catheter and in early stages, potentially thrombosis. So, we look at me arterial blood pressure. It's really easy and accessible to all practises, and we, you know, we can do this through, indirect, .

Arterial blood pressure monitoring, the speedometers, or your Machines, as well as looking at urine output, and this mixed venous oxygen saturation. So if you've got your blood gas monitors, and we don't need to be taking, arterial samples, we take venous samples, to assess that. I am as well as ama grip.

And left off here as well as our lap, that's a big thing, and we'll go through that and the fluids. So I mentioned there's these bundles, there's 7 bundles in total, and the surviving sepsis guidelines suggest that they should be initiated within an hour of presenting as a sepsis case or suspension, suspecting these cases have been. Septic, and that is to measure the serum lactate and perform blood cultures, .

Initiate broad spectrum antibiotics within the hour, and treat hypertension, . And increased lactate with IV fluids. Administer vasopressors if you cannot maintain your blood pressure, so it's hypertension again.

And I Ensuring our central venous pressure is above 8 millimetres of mercury. So, most importantly with these patients, fluid therapy, you know, this is going to increase, your blood pressure, so reduce that hypertension, as well as hopefully decrease that lactate, that's often found with our septic patients. So short wide board catheter should be placed fluid administration.

Remember to be aseptic with these patients when placing these, which should be with all patients, but especially with these patients which take particular care. So we talked about, a jugular catheter would be great for assessing the central venous pressure, but we do need to consider this coagulation as well as Our capabilities within practise to have the jugular catheter in. So if you've got, staff that aren't familiar with jugular catheter care, just considering whether that patient is going to be on shift with with those people and whether that's appropriate, especially the septic patients.

Most patients of these, seps with sepsis are going to show these signs of shocks. We talked about this, you know, tachycardia, tachy, and, these bound impulses, potential pulse deficits, but they may also have an element of dehydration depending on their condition. So just remembering that we need to replace both and within shock, we want to replace it quickly, so within.

Hours, whereas dehydration, we can sort of make a plan for, you know, 12 to 24 hours. Again, with fluid therapy, remembering our patients, underlying conditions. So if this patient has got, say endocarditis, we don't want to be, Throwing tonnes of fluids at these patients, maybe picking up a fluid therapy appropriately, you know, if this patient isn't dehydrated, could we give this patient hypertonic saline and to reduce the amount of fluid that we need rather than burning lots of crystal fluids in them.

So short doses are 7 to 90 mL per kilo in dogs and 45 to 60 mL per kilo in cats. So we don't give all that at once. It's not recommended anymore.

We kind of split this into small boluuses, and what we do is measure the response, to the small bolus, so 10 to 20 mL per kilo in dogs, and 5 to 10, in cats. We can go up to 10 to 20 cats and again, 20 to 13 dogs per sort of bolus, but we need to be really careful with measuring our fluid resuscitation. So monitoring our main blood pressure and monitoring that lactate after every bolus, monitoring our, you know, our main vitals, so, heart rate, pulses, pulse quality and respiratory, you know, really having a good listen to the chest as well.

So our goals in this, this is all about early goal directed therapy. We need to have some goals, and so hemodynamic stability obviously is what we want, but we really want to have figures, so that we can sort of assess whether we've reached, that goal directed therapy, and then what that means for our patients after that. So central venous pressure of 8 to 12 millimetres mercury or a mean arterial pressure of above or equal to 65 millimetres mercury.

That doesn't seem like a lot, and obviously most patients we aim to have our mean arterial blood pressure over, you know, 70 to 80 millimetre mercury. But in these patients, it can be particularly difficult, when their blood pressure bottoms, bottoms out, that we need to just increase it to 65 basically just to keep them alive, . So, urine output, again, is another, goal that we can look at, that's quantifiable.

And that's more than or equal to 0.5 mL per kilo per hour. And then again, another one that we could use is central venous as cranial vena cava oxygen saturation of more or equal to 70%, but that's unlikely that we're gonna be doing that one, unless we've got a jugular catheter, and central venous pressure monitoring on.

So if there isn't a response to therapy, consider CAT scans, so consider these point of care ultrasound scans to see if there's fluid that's sac. So these patients might be in shock and dehydrated and once you stop, once you stop giving them fluid bolus, . It starts 3rd space in.

And these patients are still going to be in shock. So, you know, these are another good thing to quantifiably measure, whether those, you know, if you have got free fluid and you're giving more shock bolus, you can measure the areas, so that you can see if that fluid is increasing as well, because you may have an active flu, especially with . Hypercoagulability.

So patients may have some form of distributive shock, and in which case this is where vasopressants may be needed to help increase the blood pressure to equal to or above 65 millimetres mercury you mean arterial pressure. So early goal direct therapy for iron oppressor agents, early use is recommended in the surviving sepsis guidelines. So usually we don't quickly, reach for our iron oppressor agents.

We, You know, we'll, we'll try fluid therapy, and, and continue with that. But if your target and fluid resuscitation parameters can't be achieved with these crystalloids alone. And the vasopressory therapy is recommended.

So they used to, think that dopamine was an acceptable initial therapy, and it has an ionotropic effect, . But it's kind of fallen out of favour, and norepinephrine is now the first choice of vasopressor agent. So norepinephrine will redirect the blood flow from peripheral circulation to the central circulation because it's an alpha receptor agonist, and so it's going to make it a potent constrictor of arteries and veins.

We would administer this in, a constant rate infusion, intravenously, and it does require a bit more aggressive monitoring of patient perfusion parameters, so heart rate and blood pressure. It can range from 0.1 to 2 mcg per kilogramme per minute, but often we just go for the lower dose.

But again, what we're looking for is that target mean arterial pressure, of above 65 millimetres of mercury. So now is antibiotics. So, mortality significantly increases for every hour of delay before the start of antibiotic therapy.

So, really early empiric, antibiosis improves survival. If the microorganism source can be identified, samples should be aseptically obtained and submitted for culture and sensitivity. So we're looking at blood culture samples, you know, potentially we're doing, point of care ultrasounds, or we've got somebody that's doing a full sonography for us, and taking cytology of any areas or if we're in theatre, you know, taking swabs, .

Are going to help us to identify this microorganism source, and then we can specify our antibiotics to this source. So typical first line is gonna be so your ampicillins and then refloxacin, or cefazolin and cefluxamine, or clindamycin and then refloxacin, and usually treat these for 1 to 2 weeks with these antibiotics. But the goal is to intravenous empirical and antimicrobial therapy, and it's directed to all potential infection sources, and it should be given as early as possible.

So usually, you know, nowadays we were, I'm led away from throwing lots of antibiotics at patients, but with these patients, the, the train of thought is that We give them all, you know, we give them gramme positive and negative cover, and it should include Staphylococcus, streptococcus, and E. Coli. And if we then have a, a source that's identified, via culture and sensitivity.

We can then de-escalate those antibiotics, but really getting those early empirical, at that early empirical therapy is key in these patients. And any infectious process requiring surgical drainage or debridement should be treated promptly. So obviously our goal directed therapy for these, we start this within an hour, but then we can sort of monitor our white blood cell count and our band neutrophil in response to these, antibiotics.

So another early goal directed therapy is our oxygenation. So this mixed, This makes venous oxygenation of more than 70%, . So we can use our .

I We can look at blood gases and these PAO2 FIO2 or we can look at You know, the methods of monitoring oxygen, our pulse oximetry, but distributive shock may if you, may affect perfusion and oxygenation. So it's really, important to remember that in our patients, . Especially when we're looking at things like our pulse oximetry, as well as our PCV obviously potentially being decreased from dehydration or from condition .

Sorry, not from dehydration, from, underlying conditions, from bleeding, from, haemorrhage, from hypercoagulability, and so in which case we're gonna have this decrease in, this mixed venous oxygenation. We may have dysoxia, so altered cellular oxygen consumption, . And in all of these cases, and if we can't maintain this, 70% or above a mechanical ventilation might be indicated in our patients.

So this is another case of just monitoring. Our patients respiratory, you know, as well as monitoring their blood gases, . The pulse oximetry, the response to any oxygen therapy that you give them, .

Are all gonna point towards mechanical ventilation if necessary. So just a quick note on gastrointestinal support. I said earlier that we potentially with sepsis, we can get this leaky gastrointestinal system, as well as we can get third spacing from the gastrointestinal system as well.

And often with sepsis, we do get things like GI ulceration. So use of his histamine to antagonists, so our anitidines and things like that, and proton pump inhibitors, so omeprazole may help to reduce this risk of ulceration, . They lean more towards histamine to antagonists first before reaching for proton pump inhibitors, but if you've got signs of, if you've got vomiting or if you've got regurgitation in your patients, and then add a proton pump inhibitor is hopefully gonna help to reduce the risk of this ulceration.

If there's evidence of gastrointestinal haemorrhage, you know, so we've got millenia or, we've got, you know, this third based of fluids, we've got hemorrhagic diarrhoea, . Then sort of calfrate, so teps in 1 to 5 mL 3 times a day is indicated and to give this by oral tube if needed, . Nutrition, as with a lot of conditions, is key to maximising the healing, and enter nutrition is obviously the best choice.

These patients might not want to eat, despite adequate GI protective and antiemetic drugs. So we might need to consider feeding tubes, and with this, we want to consider, The choices, especially with our coagulation profile. So, you know, we don't necessarily want to be placed in esophageal tubes and if our patients have got altered coagulation states.

But if we can't get any feeding tubes in our patients, then total parental nutrition is also acceptable. But just remembering this is going to increase our risk of infection in our patients as well. So remembering that there's two phases and if we're in that hypercoagulable, hyperinflammatory phase, .

That potentially these patients, . Are gonna have this increased risk of, of secondary infection anyway, so introducing total parental nutrition may hinder in this case. So what we're monitoring for is our urine output, thermal regulation, glucose regulation, pain assessment, blood pressure monitoring, central venous pressure monitoring, our lactate monitoring, and these are all things that we're gonna be looking at, so urine output obviously is gonna assess our.

Fluid therapy, and how successful that is, . And potentially might highlight any renal injuries, so any acute kidney injury that we often see, they often go hand in hand with sepsis. Thermal regulation, just remembering obviously these patients are at risk of, pyorexia, and we can monitor the response to, antibiosis through this thermal regulation as well, .

You know, giving these patients active cooling methods, so. Ice packs, potentially funds, . And then glucose regulation, so with sepsis, we'll often get a depletion of glucose.

And this is often one of the first signs that our patients that we really pick up that, that we suspect they have, sepsis and we get this decreasing glucose. So often these patients will need, They'll need a glucose CRI, again, just remembering, and that's also gonna increase this risk of introduction of, you know, further infection. So just keeping those IVs really clean and changing them, you know, using a, a scale.

Just to monitor whether they need changing, and everyone, you know. Performing strict as sepsis when handling, the patient in general, but especially with any, tubes or IV lines. Pain assessments.

So often these patients will be in pain, whether it's because of their underlying, whether it's because of their underlying. Condition, or whether it's just a, almost just an all over body because, you know, they get this organ dysfunction, . They'll That potentially show signs of pain.

So it's important to have a pain assessment score system, and have all your team on board with how you're going to assess these patients, what, what key things you're looking for, and just making sure it's consistent. And blood pressure monitoring. So KI monitors are really useful for these patients, .

In septic patients, often what you want is somebody with that patient at all times, but having a cage side monitor sort of, will assist in that. You can have somebody popping and looking on that patient, . Frequently but not sitting with it all the time because you can see the blood pressure monitor, you can see the ECG, and it'll pull up any, figures, but particularly in that early, that early girl directed therapy where, we're potentially using vasopressors, we want to be constantly blood pressure monitoring.

Remembering that with blood pressure monitors is particularly these indirect ones is that we want to move the . The band, either change legs, move it around, and take it off every now and again because we don't want to give that patient sort of necrosis of the tissue around where it is, because these patients as well are at high risk of edoema and especially joint swelling, and peripheral swelling. So if these patients start to get peripheral edoema and just considering where you're going to do your blood pressure monitoring from.

I'm So what we're looking for this early goal direct therapy, the end points, our secondary treatment or endpoints as we call them, and for the 1st 6 hours. What we're looking for in our patients is that we're going to have an more than or equal to 36.6 degrees, in 1 hour, if they've got a low temperature, or normalisation within 4 hours.

So what we're looking for is that temperature to come down. Or to increase if you've got a low temperature. And normalisation within the 1st 4 hours.

We're looking for a 10% lactate clearance in 6 hours. So, as I said earlier, lactate is really important and it's a biomarker, for sepsis. So if we can get this lactate to come down, we've got evidence, that's, .

Specific tooth biomarkers. That this patient sepsis hopefully improving and it's mortality is improving. A systemic blood pressure of over 100 millimetres of mercury, and a mean arterial blood pressure of over 65 millimetres of mercury.

I A urine output of 5.5 mL per kg per hour, so there's an hour missing from that. And then central venous pressure of 8 to 12 millimetres mercury put up for dogs, or 8 to 10 millimetres mercury for cats.

This mixed venous oxygen saturation above 70 degrees at 70%. And then we can do a lactate curve, which is going to time with this 10% lactate clearance, just the same as we would do like with a glucose curve, so that we can see this down. Down with spiral if I'm locked up.

I just wanted to go over a few things that human medicine are doing, in sepsis, and what, you know, that could potentially mean for veterinary in the future if these become sort of a . Part of the sepsis guidelines. So this, drug alpha, this activated one, so basically exerts an anti-inflammatory effects, and inhibits the cytokine production in monocytes.

So it decreased mortality in humans and there's a study in 2001, or Bernard at all, . And there was support for it to be used in sepsis, but there is some, controversy in using this. Macrophage migration inhibitory factor, so this activates pro-inflammatory cytokines in patients with sepsis, .

So, it is inhibits this microphage response. Nitric oxide synthesis inhibitor. So, nitric oxide produces, severe vasodilation and hypertension.

And so this, synth synthase inhibitor, we hope to sort of block this and achieve resolution. Venous philtres kind of do what they say on the tin, and they're gonna help, stop thromboembolisms, from forming. And a cysteine, and so NAC, precursor, so the precursor of this, .

Has an antioxidant capabilities, and so hopefully it would improve liver function is what they think, and reduction of adhesion of the cytokines, so hopefully you wouldn't get that cytokine storm. Occurring. And then vasopressin, so we're kind of using vasopressors now in veterinary, but it's really well advocated in humans and to increases, meal your blood pressure.

And as well as that I've got reports of having fibrilllotic activity, which can be useful in the treatment of shock, and septic shock. So that is the end of tonight's webinar, and if you've got any questions, I'll take those now. Chloe, thank you very much.

That was very informative and it's nice to have it all sort of put together in a, in a nice guided manner of things that we should be looking for and, and things that we should be doing. Just to, we haven't had any questions come through yet. I'm sure there will be some, but in, what is your feeling, and I suppose it's hard to give an answer, but, you know, once we've got, one of these septic patients, I guess it's time dependent on success rates of treatment.

Yeah, 100%. So that's what the early goal directed therapy, everything should start, you know, we should be implementing everything sort of within an hour, and really we've got our end points at, 6 hours. Within that 6 hours we should have looked at our treatment, changed our treatment several times, and.

You know, by the, by the end of that 6 hours we should sort of see a picture of our patients of, you know, potentially whether we've got a more grave diagnosis than another septic patient that we might see, you know, whether it've been really poorly responsive to all that treatment and you've got to the end of that 6 hours and you're not quite at those end goals, and, you know, that patient potentially is, you know, it's morbidity, is, is gonna be high. Yeah, and they're often quite heartbreaking because you, you pour a lot of effort into these cases and and yeah, you don't always get, get back the results, which is sad for the owners, but it's also hard as a as a clinician. Yeah, definitely, and I think, I think actually it's quite good having these endpoint goals, .

And these specific things that we can do for our patient, because I think then we kind of know that we went through the process, and that we know that we're not going to be chasing, chasing something that eventually is gonna, you know, come in. That they're not going to be well in the end, you know, at least that we can say, you know, we can give sort of a quantifiable measure to those owners that, OK, well this is, you know, if it's not reached these end goals by 6 hours, then unfortunately, you know, we've got a very grave prognosis and, you know, rather than some, you know, some disease processes and cases you see, you know, go on for days and days and days and there's never really any sort of change or end goal to them and that's so specific as. Sepsis.

Yeah, yeah. I, I must say I, I really liked your 10% lactate clearance in 6 hours. I mean, we, we use lactate a lot and it's, it's always this, you know, it's got to get better, it's got to get better.

But if you had asked me before tonight's webinar, how much do you want in what time? I, I really don't think I could have given you that answer. So 10% in 6 hours is, is really nice to have as a, a figure in your head.

Yeah, I think that's, you know, I think, it's good to have that figure, and it's important as well to remember that, you know, if you've got other disease processes, you know, it's not, it's never going to come down and like straight away. I think that's the thing, you know, that we see with other cases like GDVs that we expect we give all this fluid and we expect this lactate to all of a sudden drop. You know, it does take a little bit of time to come down, .

Even with the aggressive fluid therapy, so it's just important to remember that that we're not, you know, it used to be that, you know, if you had a lactate of over 8, everyone, you know, would, you know, it sort of be grave prognosis for that patient, but we see now if they get that 10% drop that, you know, potentially have a good, you know, a good chance of survival. Yeah, absolutely, and I'm sitting here smiling because Yeah, I think there were many cases, as you say, that you, you get this lactate, you look at it and you go, oh my God, 8.2, and you kind of think, oh, well, what's the point of trying.

But it, it, it, over the years, we've, we've got to realise that you can't look at lactate on its own. It's got to be part of a measurement and if it's improving, you've got a chance. But I just love this 10% in 6 hours.

It's, it's quantifiable, you know. Yeah, I think, I've put a link in the notes, but, the surviving sepsis guidelines are really interesting, and, you know, really interested in the on lactate, and how, how that's a really important biomarker for, . For, you know, monitoring sepsis and seeing whether these patients are, you know, got a growth prognosis or not.

Yeah, yeah. Well, that's fantastic. Chloe, we've got no other questions coming through.

It looks like I've answered all or asked all the ones. So, it's just up to me to thank you for your time tonight and, you know, we, we really do appreciate it and you know, especially having a new baby on your hands, it's, it's really lovely that you, you've given up some time to be with us and to share your knowledge with us. So thank you so much for that and congratulations on the little one.

Thank you. Thank you very much for having me. Folks, that's it for tonight.

Thank you for attending another member's webinar and to my controller Holly in the background, thank you for all your help in making it all work seamlessly and from myself, Bruce Stevenson, it's good night.