Thank you, Beth. Thanks, everyone, for being here. You all seem so spread out. I like it when we're all like a little family, all, you know, chubby together. Although, the temperature of this room, we are all going to have to huddle for warmth. So, I think by about three o'clock, we are all going to be just in this section, but that's just an observation. All right, I want an honest vote now. Who checked in for the pool and spa convention? Dr. Fletcher? This is slightly concerning that we are the only two. Very unfortunate. Anyway, you can only do what you can do. All right, so sodium disorders. This is an hour and a half of sodium. I was being, I can't decide what's worse, an hour and a half of sodium or the hour and a half of acid base, but we will, sodium is more interesting in some inherent level, I suspect. So, we'll go through this. It's sort of endless to the depth that you can take this, and so I have picked a point of which sort of some of it half physiology, half clinical, and hopefully that makes everyone, meets everyone's needs. So, for a starter, dysnatremia, one of those new words, you know, we're in that era where there seems like a new word a day. So, everything's dysnatremia, dyskalemia, just this all-encompassing term for a sodium that's out of the reference range for the species that you're in. And dysnatremia is, you know, it's a big thing now. It, within, you know, probably 15 years ago, I'd say, I don't recall this being a conversation. I'd be unlikely to have, we'd have a topic in fluid therapy about dysnatremia and treating it, but we wouldn't be having a conversation potentially in a resident level sort of physiology conversation. And so, the big change has been this association with mortality. And so, the human studies, many, many studies now have shown that there is a consistent association of an abnormal sodium concentration and an adverse outcome. And what's particularly interesting is that those associations are even true for very small abnormalities in sodium concentration. And it really is early days to know if this is a sodium abnormalities are causing the change in outcome or just a marker of severity. But we definitely felt it had been well documented in people. And then we did a study at Davis where we looked at a large number of cats and dogs through looking at a database of any animal that had a sodium concentration measured and looked and basically got very similar results to what's been done in human medicine was that an abnormal sodium concentration was associated with higher case mortality or case fatality rates. And that was true even for very small changes in sodium concentration. So this was for the hypernatremic patients or potentially this is the same graph twice. So that's going to be interesting. Let's do that again now for the... Oh, I can't work out the mouse. And same for hyponatremia, very similar findings for both cats and dogs, high and low sodium. So, it seems to be a definite thing. And then our Cornell colleagues, Dr. Goggs and Dr. Fletcher also did a similar sort of study looking at a large database and same very classic U-shaped mortality or fatality association with high or low sodium. So I feel like we know that's a true statement, that there is this association with the changes in sodium. The conversation then gets into, you know, how... Is it just an association, a disease severity marker or is there real things, bad things that sodium is doing? Interestingly, there's a few interesting things out there. There's certainly I think probably three studies that I know of in human medicine that have shown if they return that in that patient population dysnatremia is associated with adverse outcomes or greater amount of adverse outcome. And if they normalize the sodium of those patients, they can reduce their associated mortality rates or other adverse outcome markers. So it's suggestive that maybe the sodium itself is playing a role beyond just being a marker of disease. But again, I think it's a topic of ongoing investigation. If sodium is directly sort of a mechanism of adverse outcome, one of the major suggestions is it's causing that through osmotic stress to cells. Now, there are lots of other things now. It's like everything in medicine. Everything is complicated. Everything's doing a lot of different things. There's no just one pathway. So there's a lot of other things being looked at, but what sodium does in the body and why an abnormal sodium may be bad for you. But osmotic stress is certainly the big focus that has been sort of evaluated the most. So remember, osmolality is that measure of the total number of solutes in a given solution. So it's just the number of solutes. And then osmosis is the term that refers to the movement of water. You know, when you have a semipermeable membrane that's trapping solutes on either side of that membrane, osmosis is the movement of water to equilibrate that osmolality, equilibrate the number of solutes per volume of solvent. So when we talk about sodium and osmotic stress in the body, we're really talking about water shifting across membranes. And so when we talking about osmolality, total osmolality of the extracellular fluid space, there is a formula, which is your sodium plus glucose plus blood urea nitrogen, BUN. But remember that the BUN is freely diffusible across cell membranes. And so it doesn't exert an actual fluid shifting effect. It's what we call an ineffective osmol. So the ability to move water across cell membranes in the body only is going to refer to solutes, osmotically active substances. They get trapped on one side of a membrane. And tonicity is the other word we use to talk about effective osmolality. So people often use tonicity and osmolality interchangeably, but just need to be a little bit cautious about what you're talking about. So a good example is dextrose 5% in water. That fluid is a fluid that has an osmolality of about 200 and, well, this is a bad example, actually. But anyway, we'll go with it. 250 milliosmoles per liter. It's a little bit lower than the normal dog or cat. So it's not a very, it's a fairly, it's close to isoosmotic as far as infusion and what the red cells see. It's not going to cause homolysis. But that dextrose is, it doesn't, people would say that's not a fluid that really has any tonicity because that dextrose that's infused is rapidly metabolized and you don't have, it doesn't exert an osmotic effect. And so tonicity is movement. Can you, can you exert effects on water movement or not? So I don't know why, but that seems like an endlessly confusing term. So effective osmolality. So when we talk about effective osmolality in a normal animal, you could estimate it from your equation for osmolality without BUN. So two times sodium plus the effect of glucose. And so if you look in a normal animal numerically, sodium is the largest impact on the effective osmolality in the extracellular fluid space. But just one point here, which I think is easy to sort of jump on, is that it's not that sodium itself has like double the osmotic effect of glucose. It's not that it's twice as powerful. We double, sodium is times two is because this is the number of molecules in the extracellular fluid space. And for every cation, there has to be an anion. So there is, let's say 145 millimoles per liter of sodium in the average dog's extracellular fluid space. It's only 145 contribution to osmolality. We double it because we know for every one of those sodiums, there's an anion. So there are extra numbers of molecules. So there's, you know, 110 of chloride and 20 something of bicarb. So instead of adding all the little anions up and making a very big equation, we just double sodium. So the two take home points there is that sodium is not doubly effective in osmolality. Osmolality is numbers. You can only be one number. And the anions count. So chloride is osmotically active and bicarb is osmotically active. But we don't stick them in the equation just for simplicity sakes. It's not that we know, it's not the implication is not that anions don't impact your osmolality. You have a diagram for your distribution of total body water. It should be a diagram we all know and love. Tells us that in a normal animal, that about two thirds of their total body water is in the intracellular space and one third is extracellular. And it is the cells that intracellular water is surrounded by semi-permeable membrane, that cell membrane that allows water to freely cross lots and lots of water channels, but controls the solute on either side through pumps, in particular the sodium potassium ATPase pump. And so we know now from that sort of modeling that water is always going to shift, as long as it's a semi-permeable membrane, as long as it's permeable to the water, water is always going to shift to equilibrate osmolality. So if you know the osmolality of an animal's extracellular fluid, it's blood let's say, then you know the osmolality of its extracellular fluid, you know the osmolality of the intracellular fluid, assuming time for equilibration has occurred. So water will always move to equilibrate osmolality across all compartments. And again, sodium is a major player in what's determining extracellular fluid osmolality and so ultimately can have very important impact on water shifts either in or out of cells. So ultimately, this osmotic stress, why would sodium be bad for you if you have an abnormal sodium? And this concept of osmotic stress really is a reflection on cell changes in cell volume. That if you have an abnormal sodium concentration, then potentially that means you have abnormal extracellular fluid osmolality in most settings, with some exceptions to that rule, but in most settings. And as a consequence, you potentially have abnormal intracellular volume and that that is not good for cells and cells don't like having, being at abnormal volumes and don't potentially operate as well as they should. Osmolality is important. Cell volume, you know, you die if your cell volume is very abnormal. So osmolality is very important and so we have this really tight regulation of essentially blood osmolality, but ultimately extracellular fluid osmolality through osmoreceptors in the hypothalamus. And those osmoreceptors detect tiny changes in circulating osmolality. So they say, you know, 1% change will be detected. So if your osmolality increases by 1%, you go and eat, you know, a bag of salty chips and you've, you know, increased your osmolality, you will very, very quickly have a central drive for thirst and you'll have the release of any diuretic hormone and so hopefully you'll drink water, your kidneys will avidly retain that water and you will return your serum osmolality back to a more appropriate value. So when we talk in a little bit about mechanisms of dysnatremia, this response with anti-diuretic hormone becomes a really common mechanism for how we get into abnormal sodium concentrations. So that role of anti-diuretic hormone is one that we're going to continue to talk about. So there's lots of studies now that show that you can't learn for more than 10 to 15 minutes at a time and you need lots of breaks and that amazingly a break of a very short period resets the clock and then you can learn for another 10 or 15 minutes. Thereby we can justify lecturing at you for eight hours and hope that you learn something. So let's hope that that's a true statement. I have a personal interest I guess in sharks. I've always liked sharks and there's some fascinating stories out there about them. But the name of this game is I've got a collection of shark photos I'm going to show you in this talk and another talk. Is the image fake or real? In this day and age there's a lot of fake images out there. We think real or fake? This guy patting the nose of a great white. There's some fakes going on. If I tell you the photos taken in Australia I don't know if that's going to change your mind or not. But this is off the south coast of Australia, of South Australia. There is a lot of great whites there and there is this guy and I think he may take fishing, they're fishing tours but he's got into this thing where he'll chum for sharks and then when they breach he prides himself on getting his hands on them. And you're welcome to do so as well apparently if you go on that tour. So just sign me up. Terrifying. But I think sharks are sort of very inhampered in what they can do. So as long as you're behind them I think apparently it's quite safe. We'll see. Alright so osmotic stress. Osmotic stress like I said you know there's changes in cell volume you know it's an issue we think. We know it's not good for cells. And the sort of overall sort of picture that I gave you of that you know we're changing cell, we're changing extracellular fluid space osmolality and then that's directly impacting water moving in and out of cells is a thing for all the cells in the body. What's a little bit different is exactly where that osmotic sort of where that semi-permeable membrane that dictates osmotic water shifts occurs in the brain versus the rest of the body. So everything but the brain, the interstitial fluid equilibrates directly with blood. So if you know the sodium of blood you know the sodium of the interstitial fluid. You know the osmolality of the interstitial fluid you know what's going to happen at the level of the cell membrane. And that's because there's lots of clefts for sodiums and electrolytes to move across capillaries throughout the system except for when we get to the blood-brain barrier. At the level of the blood-brain barrier it is not freely permeable to sodium and many of the other ions. And so changes in blood osmolality, let's say sodium concentration in the blood is actually not necessarily equilibrated with the interstitium of the brain. And so that means there's certainly it's going to exert there's still water movement. It's going to exert osmotic force. Water is going to flux in and out of the brain but it's not just fluxing in and out of brain cells. It's fluxing in and out of the interstitium of the brain. So now that whole organs water content is going to increase or decrease with a change in sodium not just the cells themselves. So that's considered to be one of the two big reasons why the brain is the big problem when we have dysnatremia. One is the fact that we are not just altering brain cell volume which seems inherently a bad thing. We're altering the entire organ volume. But then of course we've encased the brain in this cranium that is a non-expansible system and so changes in volume are not tolerated well in that brain whereas changes in the volume of a kidney per se although all the nephrologists in the room are going to be like crying when I say this. It's not good but it's not quite the end of the world that it happens to a brain personally. Rather it happened to my kidney. So of course if we had a situation where we have a sudden increase in the osmolality of the let's say extracellular fluid and blood of an animal person then we're going to predict that there's going to be water shifting out of the cells and into the blood and extracellular fluid of that individual to equilibrate osmolality so that both the intracellular and extracellular fluid is going to come to a new equilibrium at a higher value than it was before. Loss of volume from cells is going to cause cell shrinkage and there's evidence of cytoskeletal changes of cells when this occurs so the cell sort of architecture changes. And then if we're talking about on a whole brain level if you get enough of a shrinkage in volume of the brain it pulls away from the dura and so you can actually get disruption of blood vessels and hemorrhage and ischemic damage so globally the brain can see quite significant insults beyond just the volume changes of the cells and tissue itself. In contrast if we have a drop in osmolality, a severe hypoosmolar situation then we're going to see the opposite where water is now shifting into the cells to equilibrate osmolality so that both compartments are going to equilibrate to a value lower than you were before. So those cells are going to be swelling and potentially in extreme situations you can create cell rupture but it's usually you know just generalized edema that we're worried about in particular of the brain and at worst case scenario for the brain would ultimately be brain herniation. So acute severe dysnetremia, we're going to talk about just dysnetremia concepts as far as the clinical sort of implications as a general thing so all dysnetremia and then I'm going to go through hyper, I should just say it, high sodium and low sodium because apparently after many years people tell me they have no idea what I've been saying for the last 20 years so high or low sodium separately after that but general concepts for an acute severe abnormal sodium. Acute is defined in the medical literature for dysnetremia as a sodium abnormality of less than 48 hours in duration. The likelihood is that you're going to get a sudden and significant change in brain cell volume. This is a severe change in sodium so significant enough that you're going to see brain volume changes and it's going to be associated then with acute neurologic signs and has the potential to be rapidly fatal if it's someone doesn't come along and intervene quickly. Chronic severe dysnetremia is a different ball game and so this is a sodium abnormality that has occurred more slowly. It's taken longer to get to the value that you're at. It's defined as greater than 48 hours in duration and the difference being that as long as it occurred slowly enough that you had cell adaptation then you could potentially have a patient that has a very abnormal sodium but is neurologically actually very normal and so that setting, our fear is that it's our treatment now where we could get into trouble. One thing I will say is that I was always sort of taught that as long as animals had time and people had time to adjust to a severe, generally we're talking about low sodiums most commonly, a severely low sodium then you're basically normal. You've done cell adaptation which we'll talk about in a moment but there are studies in people, there's a couple of studies that are geriatric sort of people in nursing homes. Honestly it's terrifying the abnormalities they find in these people in nursing homes. I think they check them like once every two years and they're like horrified at what's happened in the time. And so it's very common that they see a hypo low sodium in geriatric people and when they look at the ones that have been living with, you know, sodium is 110 range. So they're effectively normal but when they actually study them and compare them to similar people, elderly people with normal sodium, they have significantly greater number of falls and coordination challenges. So it is possible that this like, as long as you've got cell adaptation you're totally normal, may not be totally true. I think that again comes back to this idea that why is dysnetremia associated with an adverse outcome? Well potentially it is that although you can keep yourself alive with chronic dysnetremia, you're probably operating in a situation that's not totally normal for ideal function. So cell adaptation, this is all about the idea that it's very, very bad for cells to operate at an abnormal volume and so we have all these protective mechanisms to try and return cells back to the volume that they should be at to optimize or best case sort of scenario for cell function. They do this by moving osmotically active substances in or out of the cell or creating or destroying osmotically active substances to essentially target an osmolality that will allow that cell to be the correct volume given what the surrounding osmolality is, what the milieu is at. This is an almost immediate effect. The moment there's dysnetremia, cells start to change osmolites is the new term, osmotically active substances, some of them are electrolytes, to immediately try and protect themselves. But they really have some substantial changes that can be made that can actually save themselves in the face of very severe dysnetremia but those sort of full adaptation is slow and takes somewhere in the order of 48 hours-ish, hence the cutoff for acute versus chronic dysnetremia in the medical literature. So immediately the first thing that happens is the movement of electrolytes and so with the moment that cells sense changes in cell volume and we're always sort of focused on brain cells here, it is the movement of electrolytes either in or out quickly shuttling them to try and change a cell volume. So if you had a sudden low sodium state, a sudden hypoosmolality and their cells are swollen, then they're going to ditch electrolytes as fast as they can to try and drop their cell volume at least a little bit. And then over time if their problem is that they're too big, they're going to start getting rid of other osmotically active substances. So you know amino acids, minor Nostal, there's many, these are the ones on the slide are the classic ones that are discussed but there are many out there. And then the reverse is going to happen if you have cell shrinkage. If there's cell shrinkage, you're going to make new osmotically active substances. So you're going to translocate as much electrolytes into the cell as you can and then you're going to start to manufacture new taurine, a new minor Nostal and chop up big, bigger molecules into little molecules so they're more osmotically active. But all of that is what takes hours to days to have any full effect. But theoretically by 48 hours, the cells have got themselves back towards a cell volume that is somewhat similar to normal despite this very abnormal surrounding osmolality. And this is just a pretty picture we don't need to look at. So ultimately what are we worried about? We're really, you know I think there's lots of subtle things we're going to find out that's very bad for you when you have abnormal sodium. But at this point in time at the big picture and certainly for us as animal doctors, I think for us the big thing we are concerned about are neurologically, neurologic outcomes. They're the things we can see and potentially can have dire consequences for our patients. And so the two big scenarios are sort of what the, if all goes wrong with dysnatremia, it's either cerebral edema or demyelinating syndrome. Two sort of outcomes that we're hoping or osmotic demyelination syndrome to be correct. We're hoping to avoid cerebral edema. Cerebral edema is going to be a relatively acute change in the brain any time that there's going to be a sudden drop in osmolality. So this could be acute onset of a low sodium, acute hyponatremia. Or it could also happen if the patient has had chronic hyper high sodium and you've come along and dropped it too quickly. So in either scenario, a rapid drop in extracellular and blood osmolality can result in cerebral edema, it's going to happen rapidly. You're going to see neurologic signs as you're doing it or as it's happened. And you know, hopefully the good news is you've got, you can recognize the situation and can intervene and rectify that situation. Osmotic demyelination syndrome is the outcome of rapid increases in serum sodium. And so the most commonly described with patients with chronic low sodium that are rapidly restored to normal, too rapidly restored to normal, but has also been described in a few cases in people with acute high sodiums. So that rapid normal to high has also triggered it. So it's a sudden increase in osmolality that is the trigger and it is essentially demyelination of any portion of the central nervous system. We used to call this central pontine demyelinalysis or demyelination and because it did seem to really focus around the pons. But they've really, they've seen now that it can be, it's variable between individuals and it can be any portion of the central nervous system. So they've gone for that broader term of osmotic demyelination syndrome. And the sort of somewhat disturbing effect that, you know, we tell vet students and then they don't sleep for a week is that, you know, this is the problem with this one is that we may cause the problem with our therapy, but we don't realize that problem has occurred until days later. So it's a slow onset, you see no real time signs. And so for severe hyponatremia, chronic hyponatremia in people, they did, they talk about a two phase response where you treat them a little bit too quickly. And initially the people feel a lot better and there's an improvement. And then there's a decline at a later point in time from demyelination. And there is a subset of people that have permanent neurologic sequelae. It's very often movement disorders that they get and coordination. So this is a little dog. This little dog went to his regular vet and was in Addison's, has a hypoadrenocortisism. They're machine, they couldn't get a value. They just know he was, sodium was less than 110, but they couldn't actually get an exact value. He was treated with some fluids, but primarily DOCP. And interestingly, I don't, I guess it's not a very common situation, but he got two doses of DOCP in a sort of 24 hour period. And then came to us three days after his initial presentation, looking like this. So we just sort of didn't really interact with us at all. He was quite twitchy and tremory and he really was just like nobody was home. Our neurologists localized him to cerebrothalamic disease. We ultimately didn't image him because we felt like we sort of knew the answer. The owners were not keen to sort of go, you know, too crazy with him. His sodium to our presentation to us was 149. So we've believed that he had osmotic demyelination syndrome. And interestingly, he spent about a week with us and he got slightly better, but he came back like a month later. He was totally normal little dog for the best of our ability to tell. So he did appear to fully recover from that. It is well reported in the literature in dogs. We've certainly, I think once, every year we probably see one we think has this. To be honest, I don't know. Dan, have you ever seen demyelination syndrome in a cat? Anyone seen a cat, Shane? I've never seen, I don't know of a case report of a cat and off the top of my head, I can't think of cats. So, you know, cats do everything differently. So clearly this is maybe a different situation. All right. Now the shark photo, real or fake? This one I think is more obvious. This is a fake. This is actually the original Jaws poster. And so this is real or fake? This is the real deal. So this is a photographer who took a photo of this great white trying to recreate the original Jaws poster, which he did pretty well with. The real one is somehow even more terrifying. He's a lot more muscular sort of guy. They're like, oh my God, but very cool. All right. Let's talk about treatment concepts. So again, I'm going to talk about general treatment concepts for dysnatremia and then we'll talk about individual approaches to high and low sodium. What I will say is that I've extrapolated most of this, a majority of this, from the human literature. The exciting thing about dysnatremia, what's so nice is that we now have human medicine is suddenly like, you know, oh my God, it's really bad. And we should probably think about how we treat it. And, you know, they didn't, when I, when they looked at the incidence of electrolyte disorders in people, dysnatremia in hospitalized people is the most common electrolyte disorder in almost every study that I've seen. So suddenly they recognize everyone's got it. It's associated with poor outcomes and you've got to be a bit careful how you fix it. And so the good news is there's lots of guidelines that have come out that have evidence. Although we don't know the answers to all the questions and I'll tell you the bits that are still sort of slightly up in the air. But from that is sort of where I've sort of developed guidelines that I use that I'll share with you. But again, I will reiterate that these are A, extrapolated from people, somewhat, you know, maybe somewhat edited in what my interpretation is, but I will hopefully tell you which bits I made up. So in my mind, when you see a patient that has an abnormal sodium concentration, there are four big questions. Is it severe or not? Is it acute versus chronic? Is it symptomatic? And what is the underlying cause? Because this is really how you're going to develop your treatment plan and it is going to vary in given these scenarios. Severity, you know, what is severe? This is sort of a general number that we've come up with. And again, somewhat extrapolated from human studies, but essentially we've sort of arbitrarily for our studies in that decided that more than 15 millimoles per litre out of the reference range for that species on that machine, we're going to call severe. Clearly there's a little bit of clinical judgment there of, you know, the reference range itself is broad and so if that animal lives at one end or the other, there's a bit of a grey zone. But 15 below or 15 above the lower or upper reference range is a general working rule as being a suggestion. Is it symptomatic? So this is, is there, are there neural, abnormal neurologic signs? Abnormal neurologic, are there neurologic signs on presentation, you know, in conjunction with this severe dysnetremia that you think potentially is due to the dysnetremia? And theoretically it could be almost anything, but the classic signs that are certainly reported in the human literature and what I've seen clinically are twitchy, tremor-y animals, obtundation, anything from just being a little bit quiet to completely comatose, and seizures. And certainly seizuring is not an uncommon manifestation. Once you get to that point of the conversation, you go, oh I think he's got severe dysnetremia and I think it's symptomatic, then the next thing is to treat that animal and we'll have the rest of that conversation in a moment. But this is in a medical emergency and changing that animal's sodium a small amount quickly can dramatically improve outcome. So we don't care now if it's, we haven't got to acute or chronic. This, this is the same approach, whether this was an acute dysnetremia or a chronic dysnetremia. This is a symptomatic dysnetremia, so the initial emergency room management is going to be the same. And that is to change the sodium by as little as possible, but to some, some extent that improves the neurologic signs that are present. And so again, the human guidelines say usually you're going to change them in the range of three to six millimoles per liter until, and you stop as soon as their neurologic signs improve or once you've changed it by about six, that's probably enough to say you've done as much as you can with that, with that therapy and, and, and then move to the next part of the plan. So how do we do that? If you're talking about an animal with a low sodium, then that's going to be the administration of hypertonic saline. And in the human literature, they pretty universally utilize 3% when they, in the conversation with hyponatremia. You could use whatever percent you want, I think, just be, make sure that you calculate the doses accordingly. There's another nice rule of thumb from human medicine is that, you know, one to two mils per kilo of 3% hypertonic saline, so probably closer to two mils per kilo of 3% hypertonic saline, if you do the calculations works out, will rate, will increase sodium by approximately two millimoles per liter. So I quite like that as an incremental dose to do that once, maybe do that twice. Hopefully that's going to be enough to get you out of the sort of trouble that you're in. And then you can make a longer term plan. If this is an animal that has a very high sodium and is symptomatic, then you're going to have to administer a source of free water to drop that sodium by some smallish amount to hopefully make them feel better. And the human sort of medical guidelines, several of them suggest 10 mils per kilo per hour of a free water source. Given if you're just giving straight free water, that really is going to have to be dextrose 5% water if you're doing intravenous infusion. You can use sterile water, but only if you're co-infusing it with something else, otherwise you'll cause some cell damage. So I don't know, sometimes I'm not sure that this fluid rate is fast enough always, but it's a good sort of starting point for you to look at. And I'm going to show you a case in a moment where we went a bit faster than this. Again, I think there's some clinical judgment in all of this, but just I think the concept being the most important is that they're symptomatic, you need to change their sodium by a few points quickly, try and get them out of that. And what's quickly? Anywhere from 10 to 60 minutes, quoting the guidelines, depending on like how scared you are. So minutes, not hours. Now, if you've got to this point and you're like, now go back and get the history and you work it out and you go, I'm concerned that this is a chronic dysnatremia. This patient has had an abnormal sodium for greater than 48 hours, or I can't be sure that it's not chronic. Then you're now having to make a fluid plan that's going to change that animal sodium slowly. So you've done maybe your acute symptomatic treatment, you've made them feel better, but now you make a long-term fluid plan that changes the sodium slowly. And what's slowly? Generally, they're backing off, they're making it slower every time they do the guidelines. But the latest guidelines for raising a low sodium, a chronically low sodium, is attempting not to exceed 8 millimoles in a 24-hour period. When they're talking about dropping a high sodium, a chronically high sodium, they talk about maybe you can go 8 to 10 millimoles per 24 hours. So 8 is in both of those. So I decided that I'm just going to remember 8. I think the reality is it's a little, it's not easy to do this perfectly, so it's a bit of a ballpark. But if you can aim not to change sodium more than 8 in 24 hours in these chronic guys, hopefully if it's 8 to 10, you're still going to be okay. It's very easy to overshoot. And so I think aim low. The body has a tendency to try and jump in there and help you, which doesn't always help us. One of the things you have to remember now is that if you gave some emergency therapy, the animal came in with an abnormal sodium and was symptomatic, and you gave some emergency therapy, and let's say you changed their sodium by 4 at presentation to help them with their neurologic signs, and now you've determined it's a chronic dysnatremia, and you can only change it by 8 in 24 hours. That means you've only got another 4 left for that 24-hour period. So you have to count the change you do in your emergency room sort of stabilization period as part of that 24-hour plan, which doesn't often leave you with lots. The other interesting thing, and again a lot of this is really when you look at the level of evidence in human, they're basing guidelines on none of these is fantastically strong level of evidence. But when they look back over, they're really nearly all retrospective studies and people, and they look at the people that develop neurologic signs from what they believe is a too rapid of change in serum sodium. They say that it really reflects the changes per 24-hour period over a time frame and not a rate per hour. So if you make your little fluid plan and you only want to change at 8 in 24 hours, and at 12 hours you've already changed at 8, then as long as you keep it steady now for the next 12 hours so that over the total of 24 hours you only did that 8 to 10 change, then you'll be okay, supposedly, from what they can see. So it's not that it has to be a perfectly per hour, you do whatever that would be, 0.6 or something. You just do, just changing it, just changing it over time is the idea. So at least for me, my clinical sort of experience, it is very hard to do this. And so you do a therapy and it doesn't change at all and you go, oh my God, I did a lot more. And then it changes too much and then you stop and then, you know, it's a lot of adjustment. But the good news is you've got a little bit of leeway as long as you just keep an eye on changes over a bigger period of time. How many have been in a shark cage or want to be in a shark cage? True, true photo? Yeah, true photo. This is off the coast of Mexico. I think it was only like last year or so. There's a guy in that cage and so the sharks was, sharks when they open their mouth basically they can't see very well because like their mouth's open, it blocks their little eyes, they're a bit primitive animals. And so he lunged for the bait, you know, they bring him up to the cage for the photo and he misjudged and landed his head in the cage and they can't go backwards. So he just kept going forwards and came up and out. And then these, the guys on the boat ripped the lid off the shark cage, the door off the top of the shark cage so he could come out. So there's a whole amazing, there's actually a whole video if you Google this, it's well worth watching of this. I mean the poor shark's a bit cut up afterwards but I think he's okay. But he does get himself out and then they say, you don't, they don't ever talk about it and they said that then they like, it was a big pause, everyone paused and then they pulled the shark cage up and there's a shaky guy in there with his camera and he said he didn't get a photo. He's so upset that he missed his photo. Yeah, sure. How quickly do we see the clinical changes when we correct the sodium? The question is how quickly do we see the clinical changes when we correct the sodium? It's quick and I'll show you a couple of cases that show you that but it's usually quick. Well I think it really depends on what they're, if they truly have just abnormalities due to an abnormal sodium and you can change that quickly, the idea is that you're going to see that in some real time. Now some of those changes that may be chronic, they may be damaged, like there may be demyelination or something like that. So that's why I think in the human guidelines they say once you've changed by about six, you know, whatever you can do with an acute change, you'll have done. So, you know, in, I think one of the questions I've sort of had was, well why would a chronic dysnatremia be neurologic? And the thought is that maybe they're chronically, they've had a sudden, they live at a low sodium let's say and then they've had a sudden more of a drop and so you're probably just fixing that little part and so there may be some underlying neurologic damage that you're not going to fix. But what's, if it's going to respond, you're going to see the response sort of real time. Other causes of neurologic signs, and of course the other big confounder here is lots of causes of abnormal sodium is neurologic disease. So, you know, you've never, you know, you are, you may, you have that animal, I think if you've got a severe dysnatremia and an animal with neurologic signs, you should entertain the thought that they're connected and give some immediate treatment but, you know, maybe this is an animal, you know, with a brain tumor and, you know, has diabetes insipidus or something like that and so that, you know, I think you've got it there. So I think that's why, you know, the idea is you don't just keep treating that abnormal sodium. You do a bit, if you see changes and if they get better, stop or if you get to, you know, five or six change in sodium, you've done everything you can that's going to help for that sodium change side of things. All right, so now let's talk a bit more specifically about a high sodium, hyponatremia and our approach to the patient with hyponatremia. I'm not going to go through the causes to any great degree with high sodium, lots of good references out there but essentially you've got two scenarios. You've either lost water or gained sodium and so lots of ways in which we can do that including iatrogenic sodium gains and so, of course, another conversation in the dysnatremia lecture is, you know, fluids like sodium bicarbonate and hypotonic saline that we give, you know, not uncommonly. Now that they're developing these, you know, shown an association of mild dysnatremia and adverse outcomes, one of the conversations is, you know, if you give hypotonic saline, you'll jump up animal sodiums five to eight, you know, millimoles per liter depending on the dose at ten even. You know, is that actually ultimately a bad thing? And we don't know the answer to that but that's, those questions are currently sort of being asked in the human literature and hopefully there will be some stuff that will tell us whether what seems a relatively small change in a patient and that a lot of other benefits for that therapy, you know, long term are we going to find out that we need to be able to have those treatments without the concurrent change in sodium. Paintball just because it's a cute slide, I couldn't not include it. Paintball ingestion is a classic mechanism of hypernatremia or high sodium. Paintballs are very osmotic. They got a lot of like, I think it's like propylene glycol, not propylene glycol but they got some sort of sugary stuff in the paint that is very osmotic and so creates a lot of gastrointestinal water loss and they get, can get very hypernatremic. This very happy, proud golden retriever, sodium was about 179 I think when it came in and everything fluoresced. It's urine fluoresced, it's serum fluoresced, that same greeny yellow was pretty spectacular for a while there but did not appear to worry the golden retriever. So treatment for the high sodium animals, we're talking about free water administration. We're going to make, the rate is going to depend on both what the free water deficit is, how much water is that patient missing and then how fast are you comfortable changing that animal sodium. So then that's going to be how you're going to make your fluid plan. I think the major intravenous infusions that are easy, you can use a B-sterile water and dextrose 5% in water or you could use a fluid, a hypotonic fluid, a fluid like half-strength saline. You just have to then do a bit more calculations about how much of that fluid is water and be very sure that they can tolerate the volume associated with the sodium content. Some of these volumes can be quite large and you may not want to give that much crystalloid, that much salt and water to a patient if it's not dehydrated or hypovolemic. Remember oral water, if that animal is neurologically okay and especially if it's thirsty, which many of these are, a lot of animals that you would be able to treat, they might be able to do a fluid plan that's, you know, give him 200 ml, a bowl of water of 200 ml every two hours. So that's totally reasonable. The other side to this is if you have an animal with a high sodium, especially if it's not, if it's an animal that knows it's got a high sodium and is thirsty, like a brain recognizes that and you've decided it's chronic and you've come up with this very fancy plan in which you're going to lower it 8 to 10 every 24 hours, it's going to take 48 hours. It took an hour of your life to make the plan and then you find out as you were out of the room for a little while, you come back and someone gave him a big bowl of water. So remember you can't, if you're being very careful lowering an animal's sodium, you can't give them ad-lib access to water because then that's going to, well, they're going to fix their sodium all right, but it may not be how you want it fixed. Free water deficit. This is one of those equations that if I was a resident going to the exam, I would know. So this is the calculation that tells you, you know, about how much water you need to give a patient of a certain size to return their sodium back to normal. So you need to know the current patient's sodium and then the normal sodium is usually going to be the mid-normal value for the reference range you have or the target you've decided, you know, I want him to be at 150, you know, whatever, that's your, that's what the normal sodium is in this formula. It's that target sodium there. And remember to calculate total body water. We generally use 0.6 by the body weight in kilograms. So this is going to give you a volume. And if you do your weight in kilograms, it's going to give you a volume in litres of the free water deficit for an individual patient. And we'll go through an example soon. If the animal has a, what we consider an acute high sodium, less than 48 hours in duration, it's the acute ones in which the guidelines are totally hopeless, it feels like. But basically this is the statement from most of the guidelines, too rapid a correction is not known to be harmful. So nobody really knows the rates to, to drop, how fast is too fast to drop an acute sodium. There are definitely, as they cite in human medicine, case reports of sodiums being returned to normal, you know, in six to eight hours with no apparent ill effect. Certainly clinically we've done that with no apparent ill effect. And a lot of the, some of the guidelines talk about a 24 hour rate to take 24 hours to return an acute high sodium. But I certainly find that somewhat concerning and so do some of the authors in the literature in that the longer that brain is exposed to that high sodium, the more chance it's doing stuff, making, you know, changing its intracellular osmotic concentration. And so I personally like the idea that it's, it's less than 12 hours. But they should be where the guidelines give you the, we don't really know. And so it's, it's somewhat anecdotal. But I, I personally work with a less than 12 hours plan to get an animal that's a very sudden, has had a pretty recent increase in sodium back to a fairly normal value. So this is a case, this is actually one, a vet student's case and she actually gave me these slides. She did it and said, you know, if you ever get to, could do my dog, I'd love that. So Carl Jandri actually managed this case. I wasn't on at the time, but it was so typical to as a vet student, isn't it? So this is Seddon, he's a German, 12 year old German shepherd. And he, the student was home and with him and he suddenly just seemed not quite right. He had lots of diarrhea. He got a bit tremory and ataxic, a lot, seemed excessively thirsty. And she estimated that, you know, I think her roommate was home first and called her and she went home. So it was probably about four hours duration between what they think was the onset and when he arrived to see us. So we felt that that was the wrong slide. So when we looked at him, he was alert and anxious, not his usual personality. He's normally a very laid back chap. He was wanting to head press against the crash cart. So we felt like that wasn't totally normal and was quite tremory. His other vital signs were okay. We couldn't find anything abnormal on physical examination. On presentation, he had full blood work done and really the only abnormalities we found was the sodium and chloride concentration of the sodium 173 and a chloride of 145. This dog has a few chronic medical issues as all good 12 year old German shepherds probably do. And it actually had blood work with us, it was like three or four days prior to the visit where he had a normal sodium in the 140, mid 140 range. So we knew, we were pretty confident that this was a pretty recent change in sodium for this dog. So we classified him as an acute symptomatic hypernatremia and wanted to do something immediately to try and improve his neurologic symptoms. And so that rule of thumb for an immediate treatment in the emergency room was about 10 mils per kilo of free water, which would be about 400 mils of free water for him. And in an hour, which maybe would have been fine, he was given a liter of D5W over an hour. And by the end of that hour, they said he was essentially back to being a normal dog. So I certainly seem to be an effective treatment for him. Again, nobody really knows. He's an acute, so I suspect the timing here is not nearly as important. If he was chronic, I would have been checking a sodium at least halfway through that fluid plan to make sure I haven't changed it by too much in that time. You could also use your free water deficit formula to work out whether how much sodium you're going to drop a 40 kilo dog if you give it a liter and decide if you think that's okay or if that's scaring you. So you could think about that. Being an acute patient, it's a little less frightening. So his total body water deficit, no, his free water deficit on presentation when he came in with a sodium 173 calculates to be about four and a half liters. So that was using our free water deficit formula. So we knew he needed about four and a half liters to get him back to normal. We gave him a liter in the first hour, just sort of an emergency like, oh my God, let's try and make him feel better. So we've given him one liter. So we're down to three and a half liters. And so we sort of arbitrarily decided to give him 500 mils an hour of D5W for seven hours and that returned his free water deficit. He, towards the end of that, was bright enough that he probably would have been able to drink, but because he was fairly neurologic on presentation, they opted not to give him oral water for the initial 12 hours. Just given he's a 12-year-old German Shepherd, we were convinced he was going to aspirate and die. So, and he's a student's dog. So it felt like everything that could go wrong would go wrong. Some like eight hours after a presentation, he was considered neurologically normal at that point. His sodium at that point was 149. In the meantime, we'd sent the student home and said like, go around your house and find out what has happened. And we got very hard water in Davis, the town water. And so most people have water softeners. And so she found, and you put in water softeners, just straight salt, either potassium chloride or sodium chloride salt. And she found the big bag of sodium chloride salt in the garage torn open and half eaten. So he'd obviously, that's obviously what he'd ingested. This dog had sort of pica and some, you know, was like eating a foreign body a week and things. So it was obviously something about his underlying sort of issues that drove him to do that. But was a good ending for him. All right, let's talk about low sodium cases. Low sodium in general, I think is a little bit more challenging and certainly more complicated as far as sort of underlying causes and a little more scary when it comes to treatment. The first thing we have to consider when we see a patient with a significantly low serum sodium is, is this a serum sodium that's associated with a drop in blood osmolality or is it not? Because the treatment is going to be very different. So the animals that have hyper, high osmola, hyponatremia are animals that have accumulated another osmotically active substance in their extracellular fluid space and that's diluting out their sodium. And so that's classically going to be the uncontrolled diabetic, the DKA. Potentially after mannitol, but you shouldn't be giving hopefully enough mannitol to see a severe drop in sodium, but you can see a somewhat drop. Versus the animal that has a true loss of sodium. No, I'll take that back. Animal that has a true hypoosmolality drop in serum osmolality in association with their sodium. They're the ones that we're going to be worried about with our fluid therapy. So if it's a hyperosmolar, hyponatremic animal, the DKA let's say, then that brain hasn't seen a low osmolality. So it hasn't done all those cell fixie things. And as long as they're not too hyperosmolar, they're usually just mildly, then that whole osmotic aspect of the sodium is not going to be the focus of your treatment. The focus is going to be the primary disease. Now we do know that sudden changes in glucose can sometimes have central nervous system effects and maybe that's somewhat of an osmotic effect as well. But we tend to regulate, as you know, the treatments of DKAs around the rate of change in glucose and the sodium is going to fix itself once we return that sodium to normal. Now I think I took that slide out sadly, but what I would say is there are those correction formulas that allow you to estimate what the sodium will be when you return the glucose back to normal. And if what I'm saying is not something that sounds incredibly familiar, come and talk to one of us after in a break and we can give you more details on that. So you can just ballpark and say for a given glucose, when I correct this glucose, what's this animal sodium going to be? And just reassure yourself that there's not a sodium abnormality hidden under there. As long as they're going to correct to a somewhat normal number, then your treatment's going to be all about the glucose and the sodium is going to fix itself. But the hypoosmolar, hyponatremia animals are the ones in which the treatment is much more challenging, at least certainly the chronic ones I think can be. And the treatment, the actual treatment is going to depend a lot on the underlying cause. So the next step, you know, the sort of step four in that sort of the questions you have to ask yourself when you're dealing with severe dysnatremia is what is the underlying cause? Because when it comes to hyponatremia in particular, that's going to very much dictate the way in which you're going to elicit a change in sodium in that patient. So the next step is I've now, I have a patient that has a significantly low sodium. It's a hypoosmolar, hyponatremic patient. Then the next part of this would be to look at, think about what you know about the underlying disease in that patient and to assess the volume status of that animal currently. Because the mechanisms by which you've reached a low sodium state will be different and hence the treatment. What I would say is that as a general rule, there's no absolutes in medicine, but as a general rule, you don't get a low sodium. A rule out for low sodium is not sodium loss. It's always water gain. You don't, there's only one disease where sodium loss is a conversation and that's central, that's cerebral salt wasting syndrome, which is probably very rare and somewhat controversial. I'm not going to get into it because I don't have time. But beyond that scenario, I would just, when you see an animal with a low sodium, think this is a water gain. The answer, when the residents get asked like, why has he got a low sodium? The answer is always going to include the words anti-diuretic hormone, almost always. So it's just, the kidney can excrete so much water if it's doing the right thing. That generally, if you've got yourself down to a low sodium, the only way you've got there is maybe beyond the person who goes to a water drinking contest and drinks themselves, you know, a thousand water bottles in an hour, then maybe that's not anti-diuretic hormone, but most things are. So hypovolemia, uvolemia versus the hypervolemic patient that has a low sodium. Hypovolemia, hypovolemic, hypoosmolar, hypovolemic, hyponatremia. So these patients, like classically would be gastrointestinal losses, third space losses. We see this a bit when, you know, lots of, you know, that animal that gets an abdominocentesis or thoracocentesis, you know, gets a couple of liters off every few days. And then at some point somebody checks a sodium and they've got themselves down to a very low amount. This has to be the sort of hypovolemia that doesn't kill you in a few hours. This is not like hemorrhagic shock, you know, where you either die or someone fixes it. This is chronic hypovolemia that it's lasted long enough that one, you're not so bad that someone takes you to the veterinarian. And two, you're well enough to still drink some water, but you probably don't eat anything because you feel pretty bad. You've got enough volume deficit in the system that you have decreased your effective circulating volume. You've upregulated your renin, angiotensin, aldosterone system. And then in turn, that's upregulating our anti-diuretic hormone secretion. The consequences of that is that you're very thirsty and the kidney is avidly retaining salt and water. And then the last step here is that you're a sick puppy dog or maybe a cat, and all you do and you drink lots of water, you don't eat very much because you don't feel very well. So your kidney would take salt and water. It doesn't want to just retain water, but you're only giving it water to deal with. And you've had long enough to do this that you've been able to have a substantial increase in free water. Hypovolemic hyponatremia. These animals are, everything works fine. This is an appropriate response. They just haven't been able to, this is all they've had to try and salvage the situation. So volume administration is going to be your treatment here because once you give this animal appropriate volume, then its kidney is going to be like, oh my God, thank God. Get rid of all this water now. Now hypoadrenocortisism is a very classic mechanism of hyponatremia as we all know. And as I said before, you don't tend to lose sodium as a mechanism for hyponatremia because of osmoregulation and lots of other reasons. So in hypoadrenocortisism, the mechanism of the hyponatremia is actually the loss of inhibition of ADH from glucocorticoids. So there is pretty classic scenarios in people where they're hyporeninism. They don't make renin. So they don't have renin, angiotensin, aldosterone, but they still have glucocorticoids. They do not have a low sodium. So it's not the mineralocorticoid that's causing the low sodium in these patients. It's the lack of a glucocorticoid. And so these animals classically do present hypovolemic, but you can see Addisonian animals present with electrolyte abnormalities and they're not necessarily hypovolemic. But I put them in the hypovolemic category because I think it's the more common scenario that we associate with them. But this is ADH-mediated event. Everything's about ADH. Euvolemic hyponatremia. This is a pure free water gain because with free water gain, you're going to cause a low sodium, but it's very hard to increase volume, extracellular fluid volume effectively with free water gain because most of free water goes intracellular. So certainly syndrome of inappropriate ADH would be the sort of archetypal example of this where diseases and clinical abnormalities that trigger antidiuretic hormone release when it shouldn't be there. And so there are cancers that do that, but in the intensive care unit setting, that's nausea, pain, opioids, prolonged anesthesia, surgery, in particular orthopedic surgery. Essentially every animal in the hospital probably has a tendency to have inappropriate ADH on board. Neurologic disease is a really big category as well. So in some of these animals, they can, especially if they're well enough to drink water, create a hypo, a euvolemic hyponatremia. Some of the polydipsias, they know the primary polydipsia patients will fit into this category. Free water administration, for me, this is nearly always the animal, the feeding tube, hence the picture of the cat. These are those, you know, you send that, you know, medicine sends that animal home with its, you know, 20 meds twice a day and a feeding tube. And the owner is so scared about the feeding tube blocking it, they give, you know, 50 ml flush after every med twice a day. And so then they come back in and their sodium is 110. So especially in kidney disease, you don't always have the ability to excrete extra water. So you forcing more in the system can create this situation. Hypervolemic hyponatremia, this is probably most commonly for us, I think, going to be congestive heart failure. But certainly some of the renal, many of the renal diseases, you'll see this where they just, if you don't, you need a certain surface area of tubules to excrete free water. And if you don't have those, then you accumulate and you're still drinking. Then if you take in more than the kidney can excrete, you'll end up with a low sodium. Nephrotic, I've just left there, left you hanging, it's quite exciting. Nephrotic syndrome fits into the same scenario of it. So these animals have to have also gained salt because they're hypervolemic, but they've gained more water than salt. And so even though total body, their volume is greater than normal, like congestive heart failure, they've got a disproportionate gain in water and hence, overall, they've got low electrolytes. So treatment, let's just go back a slide just for this slide. So treatment-wise, the hypovolemic patient, volume administration is going to be a therapy, isotonic crystalloids, just if we think this is a chronic hyponatremia, the challenge can be that as soon as you just give them volume and restore their fluid deficit in the next six hours, their sodium will be normal in the next six to 12 hours. And so they're actually one of the hardest to restore slowly. And sometimes you have to use drugs like DDAVP to try and stop them fixing themselves too quickly. So they actually, in my experience, have been more challenging to regulate how fast they change their sodium. Euvolemia really depends on the setting. If it's the animal with the feeding tube and it's getting way too much water, then it's just a matter of slowly backing off how much water, but you reduce. If it's chronic, you just take a week to get back to where you think that animal's water admin should be. So just be very slow. But otherwise, potentially, furizomide is very beneficial. If that animal's not maximally diluting their urine, then furizomide is going to help you get rid of some of that free water as well. And then the hypervolemia diuretics is obviously the mainstay of our congestive heart failure management. And then the kidney failure is really going to depend a bit on the other aspects of kidney disease, and maybe water restriction could be part of the treatment of that animal. So they get a little bit complicated. Then there is a subset of animals that you either need to change their sodium more quickly, or they're not changing their sodium with the original therapy plan that you may need to actually give them hypotonic saline as your plan to return their sodium back to normal. And so if you're going to do an actual sodium replacement plan, you need to know, it's like the free water story, you need to determine, well, what is their sodium deficit? How much sodium does this animal need to get its sodium back to my target value? And then how quickly am I comfortable changing this sodium? And from there, you can make yourself your fluid plan for sodium. And so the sodium deficit formula is another one that's good to know. Very similar to the free water deficit formula where the patient's current sodium and then the normal sodium that I've, what I've listed as normal sodium in this formula essentially is the target value you're trying to get that patient to. So maybe this is just a 24-hour plan and you're just putting in a value you just want to be at at 24 hours, or maybe this is the total plan and you're targeting a normal sodium. You can plug anything in there to calculate in millimoles per litre. If you're doing this in body weight as kilograms, this will give you, no, not millimoles per litre, it'll just give you millimoles, the millimoles of sodium that you need to give. And I'm going to go through a case that'll hopefully make that make more sense. Now, this is where hyponatremia is a bit trickier. So how quickly can we restore an acute hyponatremia to normal? And it's a bit of a sort of nobody knows, but generally if the thought is if it's in hours, and again, what does hours mean? Everything's in hours. In my mind, at least less, certainly less than 24 hours duration, then we probably should just be getting it back to normal sooner rather than later. I've conservatively said, you know, 8 to 12 hours, but potentially even sooner. Again, the guidelines don't know, but they agree that we probably don't want the brain to see that low sodium for too long. Now, there's also that acute hyponatremia that is more than hours in duration, but it's not chronic. It's not 48 hours. And so this is that sort of 1 to 2 day duration. And maybe in veterinary medicine, it'd be hard for us to know that. But if we did know it was in that timeframe, the concern is I think that there is some change to cell osmolites. It's not full adaptation, but enough has happened that we might have to be careful. And so the guidelines suggest that you basically, you know, you go at 8 to 10 millimoles per 24 hours to restore this, even though this is a somewhat acute change. Remembering that for chronic, they say less than equal to 8. So, you know, you can go a tiny bit faster, 8 to 10 for this 1 to 2 day time window. So again, this is an area in which they just not, nobody's totally sure. There's still some, I think, work on trying to be, trying to tease out what our options are. So let me just tell you about a couple of cases. The first one's Toby, a two-year-old male Yorkshire Terrier. He had spent the last two hours playing in the swimming pool and they said he was just in and out, jumping in, swimming and in and out and in and out. And then they realized he was quite ataxic and then he sort of fell over and didn't move very much. So when he presented to us, he was collapsed. He was stuporous and twitching. Hopefully this, he shows, you can sort of tell, this is him on presentation. So it's sort of hard to tell. He is quite twitchy, but I don't think it shows very well, but clearly neurologically abnormal. And also somebody very annoyingly having a problem with the syringe cap, the needle cap. It's like, why are you doing that in my video? So anyway, this little Toby, two hours after lots of swimming in the swimming pool. No, no, let me go. So on our initial ICU panel, on his blood gas on presentation, his sodium is 126. Now Toby's basically never been to a vet before. We've got no idea what his sodium normally is, but given the history, we're assuming that this is a sudden event in which he's had just water ingestion. So he's quite neurologically abnormal. So we gave him emergency treatment on presentation. And so he's five kilos. He ended up getting five mils of 7.2% hypotonic saline, which I guess is, I don't know, 10, 12 mils. That would have been about 12, equivalent of 12 to 14 mils or 3%. So just work it out. But he got five mils of hypotonic saline, 7.2% over 20 minutes. After that therapy, like at 30 minute, you know, about the 30 minute mark, we rechecked his sodium and it was at 130. So he went from 126 to 130. And unfortunately I don't have a, well, I do have a video, but it wouldn't play. But he looked like he's very quiet, but he was, you can see him sitting there. He's much more, he's responding to us. He knew what was going on. He wasn't twitching anymore. Quite alert and interactive in that, at that 30 minute mark. So now we would need to make our sort of ongoing plan. We've done that emergency room stabilization. So now we need to work out like, let's get his sodium back to normal. So we're going to do a hypotonic saline infusion. So we wanted to know what his sodium deficit was. So we plugged all our numbers into the formula. And we're starting as of now, we're starting, I've just done the sodium deficit is now he's at 130 because we've done our first little bit. This is acute. So I'm not so worried about speed. I'm just, we're just more worried about getting him to the right number. So he has a sodium deficit left if we want to get him back to 145 of 45 millimoles. So our plan was to try and do that in less than 12 hours. And so if we gave him 45 millimoles over 12 hours, it worked out to be, what is that? 85 mils of 3% hypotonic saline over 12 hours. Um, we ended up giving, I can't remember what that hourly rate would have been, but we actually rounded down a little bit because the idea here is that this guy is a normal little dog, normal young dog with normal kidneys. He's going to be peeing out water as fast as he possibly can. So there is going to be, he's going to be trying to fix himself. And so I don't know that we're going to need to totally do this with hypotonic saline. Is it possible that he needs any, and he could just do this all himself? I think it's possible given he's neurologically abnormal. I just felt like we should maximize the chance that we get his sodium back to normal. So we did a conservative version of, of replacing that whole deficit. Um, and then just check the sodium every couple of hours to see, keep, make sure that we were going at the direction we wanted to go at. He also had a very low potassium, um, on admin, uh, admin. And so we were just monitoring that as well. Uh, he had, his sodium was normal at like eight hours. I think he, he had a normal sodium. This is him at 12 hours. He's totally normal little dude. We couldn't, it seemed totally normal to us why he stayed in the hospital. 48 hours is probably somewhat questionable, but I think we were, we were more worried than he was, uh, but he did great. All right. One more case. This is Sam. He's, um, unfortunately I don't have a video of Sam, which is one of those like, I don't know why I don't have a video of Sam, but I don't. Um, but he had lethargy and inappetence and vomiting for three days. Uh, and then this morning he had a seizure. So the owners brought him into our emergency room. Um, this is Sam on presentation. You can imagine, you know, it's not like you need to see a dog seizuring. So really, um, and on presentation, he has a sodium of 115 millimoles per liter. Now we've got no blood work on this dog anytime in the last year, so we don't know where he normally is. Um, but we did feel like, uh, he has had clinical disease for three days. So we're suspecting that this, whatever this is, is potentially he's had an abnormal sodium for three days or at least two days. He also has a pretty spectacular metabolic alkalosis. He's bicarbonate 54. Uh, he was quite dehydrated on examination and during our initial sort of emergency room evaluation, he had another seizure. Uh, so we decided that we were going to consider this to be a chronic, severe, symptomatic hyponatremia. Uh, you know, there's really no way of knowing how long his sodium has been low enough that his brain has been unhappy. But, um, given, given that setting, we felt we had to be as conservative as possible. Uh, given that he's seizuring and abundant, we gave him, um, some hypotonic saline, uh, in the first 20 minutes and he ultimately got, uh, 18 mils of 7.2% hypotonic saline, six kilo dog. And he definitely improved neurologically. He went from sort of lying there, sort of not really wanting to move when we're touching to sitting up sternally and interacting with his environment. I would still have considered him abundant, but we felt that there was obvious improvements. At the same time, we started him on lactated ringers as 60 mils an hour because he was quite dehydrated. Um, remembering that lactated ringers has a sodium of 130. So it's often a great fluid for low sodium patients because there's not very much free water in that fluid. So it's a way to be able to rehydrate a patient without getting in the way too much of your, of your fluid plan for your sodium. After he's 18 mils of hypotonic saline, his sodium was now 125. He went to abdominal ultrasound and given that raging metabolic alkalosis and some abdominal palpation, we're fairly sure he had a foreign body and they could see two large spherical foreign bodies in the proximal duodenum. Uh, so he's a hypovolemic hyponatremia. So just as we talked before, he, I think he's had foreign bodies for three plus days. So he is unable, he's not eating, he's vomiting, he's got volume loss. Um, he's upregulated his renin-angiotensin-aldosterone system. Um, he's thirsty. His brain is telling him like, dude, we need, we need water. Um, he's not eating and he's, or if he is, he's not keeping it down, but he's obviously able to absorb some water. And so he's, of what he's drinking, he's absorbing enough of it that he's given himself this very significant hyponatremia. Uh, and again, the volume induced thing needs days. You know, that doesn't, that can't happen in a couple of hours. That's going to have to have taken days to have generated that. He went to surgery and he had two little bouncy balls in his duodenum. Um, and we just kept him on lactated ringers as his fluid therapy during anesthesia and the surgical procedure. Um, because it really was very similar to where he was at. And we were, he, we feel very confident his kidneys are going to fix this very quickly. Our problem now is more about how do we like slow him down if he goes too fast. Ultimately, we sort of just let him do it at his own pace. Uh, so he's slightly faster than ideal. He started at 115 and at 36 hours, he's on 136. So he's what, 21 or something. He's in 36 hours. So he certainly exceeded the optimal of eight, uh, in a 24 hour period. Um, and you know, this is a bit of a judgment call. Again, this, you know, these volume animals are very hard to slow down. He wasn't so, so dramatically out of the sort of recommended range that we elected to allow him to go that fast. But I think this is for me, the area that I'm always unsure of just how, how much intervention we should do to try and stick to the rules. So just in summary, severe dysnetremia. First, first, I think sort of, um, important question is going to be determining if they're symptomatic versus asymptomatic. Because if they're symptomatic, it doesn't matter anything else at that point, you need to do some immediate stabilization. Once you've got them stabilized, then look, determining if they're acute or chronic and obviously going faster if they're acute and slower if they're chronic. Um, and, and using those free water deficit formulas and sodium deficit formulas to help you, um, develop some of those fluid plans. Uh, real or fake? This is, um, this is actually one of Australia's like favorite children. This is Mick Fanning. He's a world championship surfer. This is off the coast of South Australia, no, South Africa in 2015 and the world championship surfing competition. So this is all on film because he's in the surfing competition. And this is a great white. And unfortunately I couldn't get you the video, but again, a great video to Google. It's actually sort of hard to watch, but you can, like for a while, like he doesn't know the sharks there yet. You can see the shark coming out of the water, he doesn't know the sharks there yet. You can see the shark come up. He wrestles with it. He goes underwater. You're like, Oh my God, like this is the worst thing we've ever seen. He ends up punching it a few times and then they scramble over with the little jet ski and get him up on the jet ski and he's fine. But luckiest guy on earth. And the next time he doesn't, he takes like a month off surfing, comes to Australia. He lives just near where my parents live, Tweed Heads. He goes out the first day, he goes out, out behind the breakers and he looks over and there's a whacking great big shark in the water and he went straight back into shore and took another month off surfing. But he has continued to surf. He retired last year, but amazing story. You should watch the video. Any questions? Yeah. Yeah. Absolutely. Yeah, it's a great question. So the question's about this idea that we know these hypovolemic animals are going to correct themselves quickly, and then you can use DDAVP or desmopressin to essentially force them to retain free water and prevent them from correcting themselves too quickly. And then, like, when do you do that proactively versus just waiting? I've only ever done it once they've started to go too fast, and then done it sort of, you know, we're just checking sodiums every six hours, and if we're unhappy, we give them another, some more DDAVP. Saying that, what I haven't had is an animal that was in such severe hypovolemia that I, you know, really felt that I, you know, we had to, you know, we were also a bit slow in the volume administration in these patients. We haven't correct them as quickly as we correct volume in a normal sodium patient. So I think that there would be, but I could potentially see an animal with an extremely severely low sodium, so that's the other thing, 115, I'm scared, 105, I'm really, really scared, so the lower the sodium, the more volume, the deficit that I feel like I have to give quickly, then maybe I would consider giving it proactively. But clinically, personally, I've never used, I've only ever used it when I've noticed the sodium's going faster than I'm happy with, and then given it. I don't know if anyone in the audience has given it in any different form. I'm getting, no, no, no. So yeah, I haven't. But I think you could, you could argue that, but I think generally I've started to see what happens, and I mean, I think it's long, luckily, you know, we can run a sodium very quickly on a small amount of blood, as long as you've got that ability, then DDFP works very quickly. And you know, and that's the other thing is, you know, that's been shown, again, in not high level of evidence, but certainly in clinical, in human studies, they've shown that, you know, if you do overshoot, if you bump them back, so that at the end of the 24 hours, you didn't do the eight, you're okay, you know, that that's seen to be a relatively safe option versus, so having a quick overshoot and then giving them some DDFP and getting them back, supposedly gives you some safety. They're always challenging. Yeah, Tanika. The oral urethra, I have not. And I think mainly because I haven't really had a case where that I needed anything sort of long-term that would have been for an oral use. So I've read about it in the human literature, but I've never used it. I don't know if you have, but I have not ever used that. All right, our brains probably all need a break now. Go, Missy. Yeah, the comment was about the sodium concentration in other drugs we use, and I want to talk about chloride and talk about that as well. I think it is very easy to miss that there's other sources out there. Yeah, I totally agree. All right, thanks everyone.

dysnatremia

abnormal sodium concentration

adverse outcomes

case fatality rates

osmotic stress

cerebral edema

osmotic demyelination syndrome

acute dysnatremia

chronic dysnatremia

severe dysnatremia

hypotonic saline

complications