So again, now we're going to talk. The topic is hyponatremia. And can you hear me? OK, yeah, that's good. OK, so we're going to discuss hyponatremia. And oh, it already says my time is up. So anyway, just wanted to make sure the timer is right. So it's more hyponatremia for the non-nephrologist. So I was going to talk a little bit about the epidemiology of it. These are my disclosures, same as previous. A little bit about the epidemiology, the prevalence, associated complications, how do we diagnose it, and try to summarize. In the last year or so, there were three or four new clinical studies. So I focused on that to give you what's new in hyponatremia. So I'd like to start with a case. And this is a very common case. I'm sure you all have seen this. This is a 72-year-old woman. She's brought to the emergency room because she's confused, lethargic. She was on an ACE inhibitor for her blood pressure that was poorly controlled. And her primary care provider decided to start her recently on a hydrochlorothiazide. And you examine her. Her blood pressure is normal, normal heart rate. She's a febrile. She's only oriented to person. Lungs were clear, no edema. And there are no focal neurological signs. And I'm sure all of you are thinking already of what could this be. And you order your sodium. And you get a sodium of 112. There's a potassium of 3, a bicarb was 24. Her creatinine is normal, uric acid 1.5. So during the talk, we're going to discuss some of these labs and what we would do for this patient. Now here, we have a urinose molarity of 620 and urine sodium of 140. So that should help you decide what type of hyponatremia this is. OK. So first is the definition. So hyponatremia is any sodium that is less than normal. And our normal starts at 135. So less than 135 is usually what's considered. But when you read a study, you have to look at the definition. Because sometimes they have 138. Sometimes they have 135, 120 when they do studies on severe hyponatremia. So you have to look at that. So mild is considered 130 to 134. Moderate, 120 to 129. And anything less than 120 is considered severe. And most individuals with neurological changes have a serum sodium of less than 120. So hyponatremia is the most common electrolyte abnormality that we see in the hospital. So I would say when I'm on service, probably three, four, we get like two or three hyponatremia consults a day. So it's super common. If you look at the different definitions, so sodium less than 135, about 15% of everybody that's admitted has hyponatremia. And if you look at a different definition, like 138, it's almost half, so 40%, 38% of individuals. And those names there are authors. That's where I got the references from. So the most important thing to remember, and I think that is that hyponatremia is a problem of excretion of water. It's not that they don't have enough sodium. So that is the most important. And I put a nice picture that I found on the internet of the kidneys, because it is a kidney problem. The kidney is unable to handle the water for x, y, or z. And we're going to discuss some other issues on how that could be. So why do we care about hyponatremia? Well, other than it helps us all make a living, it's also very important for the patient, because it's associated, it's a predictor of mortality. And depending on the level, it's also associated with the length of stay in the hospital. So it becomes more expensive for the system, the payers. And here's a study. They pick the worst colors, because I have a hard time finding the green and the blue. But I decided that the green must be the one going up, because those are the ones that get discharged home. And that was the only way. But it was hard for me to find the blue and the green. But anyway, when you get admitted and your baseline sodium is higher than 130, for sure you're going home. But you can see that if you are in the blue, those people are the most likely to die and are the ones in the lower sodium numbers. And then next to it are people that go to hospice, also in the lower numbers, and then people that go into a nursing facility. So this is a very interesting study. They looked at 2,000 hospital admissions. I'm sorry, 2 million hospital admissions, and then divided the cohort into those that had hyponatremia and those that did not have hyponatremia. So this is the one we're focused on. And then they divided, again, different levels of hyponatremia. But you can see that there's a dose-dependent response on who dies in the hospital based on what the sodium was at admission. So obviously, if it's less than 120, they have the highest mortality. But they're also probably a sign of some underlying sickness. But they're also more likely to end up on hospice or end up in a nursing home. Then the other thing that's very important about hyponatremia is that some people have chronic hyponatremia. So we have the definition that I was discussing is the people that are hospitalized. But we have older patients, et cetera, where their sodium is low. And for a while, we thought it didn't matter. Oh, they have a reset osmostat. It's all fine. But now we're having more and more literature finding that it is associated with falls. And I'll show you another slide where those falls are associated with fractures. And so it does become important to treat those chronic asymptomatic hyponatremia. So here is a diagnosis of a fall. Oops, sorry. So those patients with hyponatremia have a 60, they're 67 times more likely to have falls compared to controls. So quite a big difference. So people in the same age group, et cetera, they fell here 5.3% versus our chronic hyponatremic patients, they fell 21%. And I like this very elegant study by this group, Renneberg, they actually did studies of dynamic tax and executive function and things like that. And here you can see that when you drink alcohol, here before and after, there was some minor differences in how they performed the tax, but not too much. So being hyponatremic, so these were patients, they took a group of patients that were being treated chronically for hyponatremia and they told them, would you stop your therapy, whether they were on furosemide or sodium tabs, whatever they were, and then do the test when you are on medication and do the test when you're not on medication. And so they looked at how they were doing. And it basically works to be a hyponatremic, they did worse. You see the higher the score, it's something about how they walk. They put some pressure on how the center of gravity is, et cetera, and so they could tell, the higher the points, the worse you're doing. And so you can see that if you're chronically hyponatremic, you do worse than if you were drinking. So very important, I thought that was very interesting. And then here, data, as I said, the risk of fractures also goes up. When your sodium is less than 135. So this is that graph, this is, I took it from an endocrinology review. But it's basically classifying hyponatremia based on serum osmolality and that's what we do. So we try to get the sodium, the urine sodium, all at the same time. So serum osmolality, urine osmolality, and sodium in the urine and the blood, all at the same time, because otherwise you cannot compare. Because same as the glucose, the sodium changes all the time based on what's going on. So based on that, we divide hyponatremia into hypotonic, isotonic, and hypertonic. Hypertonic, you're probably very familiar with, those are when people are hyperglycemic, that's where we get that. And then the isotonic are those laboratories abnormalities when the protein is very high or the lipids are very high. And if you do direct measurement, the results are normal versus if you do the indirect measurement which shows falsely high, or falsely low numbers. And so here, then we're left with our hypotonic, hyponatremia, which we're gonna continue to discuss now. That's what our patient has. So here are a number of causes of why ADH is high. So there's some that are hemodynamic, so volume depletion does this, hypotension, congestive heart failure, cirrhosis, nephrotic syndrome, adrenal insufficiency, but also there's significant number of stimuli, pain, nausea and vomit for sure, hypoglycemia, medications, being perioperative. This is super common, right? The patient comes in, they're NPO, so they're likely a little bit volume depleted. Then they have surgery, they're in pain, they become nauseous, that drives their ADH high. And then hopefully there's no surgeon here, but what do our surgeons do? They give them, at least in the US, they're in love with lactate wringer. Lactate wringer is hypotonic. And then we get a consult for hyponatremia because they gave them two liters or three liters and now they're shocked that the patient is hyponatremic. So that's like a very usual picture. And again, cancer, pulmonary disease, it could be cystic fibrosis, could be COPD, could be pneumonia, all of those are drivers of ADH. And then CNS disease, not just a tumor, but other meningiomas, masses, et cetera, can also cause it. This is not an exhaustive list, but this is one of the list of medications that cause ADH, elevation. So I usually, one of the first things we ask is, is there something new medication that you started a week ago, two weeks, three weeks, a month ago? Because frequently we can find what is the cause. Again, in our lady, obviously she started the thiazide, so that is a clue right there. But thiazide is right here. But there are all of these medications, and they're divided here. So there's AVP release stimulants or potentiators, there's some that directly are activators of AVP, some that cause this reset osmostat. Sometimes you hear that as idiopathic hyponatremia. And then other compounds like thiazides, trimetropin, that sort of increase urinary sodium. So something else that is quite important is that women are more likely to have severe disease and are more likely to get neurological deficits because of hyponatremia. So here you have everybody that was hyponatremic. If you look at everybody, women and men are fairly equal. So 54% women, 46% men. But then in the cases that had brain damage, which was less, 34, you can see that 97% of the people were women, right? And then they looked, and this is a known fact, that if you look at everybody that had the brain damage, the majority of them are young women. They're all menstruating instead of being postmenopausal. And so here, again, showing the severity between time of the hyponatremia, meaning how long they were hyponatremic, and the level of serum sodium, and how it affected their mortality. So these are deaths. So you can see that hyponatremic women with less than 24 hours, they were more likely to die compared to, let's say, men. Men is right here. And then here, with more than 24 hours, then here, women with 86 to 115, they were more likely to die than men, and same thing here. So, I didn't present it here, but there's some data that they're more likely to get cerebral edema because there's cells in the, not the brain, not the neurons, but the astral, whatever, the other one, the ones that hold the brain, they're supposed to swell. And that's why there are studies in animals where they gave testosterone, and the brain didn't swell as much as when they gave estrogen. So that's the thought behind that. Anyway, so diagnose SIADH, which is what our lady has. You have to have low serum osmolality, which we have. A urine osmolality that's greater than 100, and remember, hers was like 600-something. She has to look clinically euvolemic. And that's what she looked like. Those patients have to have urinary sodium greater than 30, because if there are less than 20, you think that the patient is either volume depleted, or they could have heart failure, or nephrotic syndrome, or something else where they're sodium avid, and now the sodium is not going into their urine. So, and then you have to look to make sure that they don't have other causes, such as glucocorticoid insufficiency, or severe hypothyroidism, and normal renal function, and absence of diuretic use, boom, boom, boom, boom, boom, particularly the thiazides diuretics. Okay, so this is now the approach to the management of SIADH. I actually thought this was funny, because they have here, but anyway, we'll start from the beginning. So, I always knew it as SIADH, but apparently the new name is Syndrome of Inappropriate Diuresis. That's at least in this review. But anyway, so we try to fluid restrict first, and there's a formula nephrologists use, measuring the urine sodium, plus the potassium, over the total body water, and it tells us if they're gonna respond, if it's less than .5, they should be on 500 fluid restriction. If it's .5 to one, then a liter should be okay. If it's greater than one, they're not gonna respond to fluid, and you have to do fluid restriction plus something else. So then, our lady, we started, let's say the fluid restriction, and she didn't improve. This is hypothetical. And so, I thought it was funny, because they have the tolvaptam, the urea, and the SGLT2, which I'm gonna mention first. But in reality, in practice, we do the third, where it says other. So we usually add more solute, right? Because remember, the urine, the water doesn't go out by itself. We need solutes to drive the water out of the kidney. So, and remember, she has a very high burden of our patient, right? Has a high burden, because her urine ossums are 600, which means that for every liter, she's dumping 600, right? So she needs 600 to dump one liter, so that we can improve her sodium. So in this case, we would probably do all of the above. We would do a loop diuretic, and we would probably give her sodium tabs, and I haven't mentioned this before, but there is a little bit of controversy versus we should do bolus or infusion of 3% saline. But in any case, going back to our lady, because she's neurologically impaired, the first thing we would do is give 3% normal saline, okay? So, but anyway, these other things are also helpful, especially if you have somebody chronically, you could try an EMPA, if it didn't work by itself, or urea, there's a new study by people from Pittsburgh, Rondon is the first author, where they gave urea and they did well. It's a little bit expensive, and some people don't like the taste, et cetera. So I don't know if you guys have experience with that. I've never used it, but it's available now. And then Tolvaptan is also available. Unfortunately, it does overcorrect a lot, and so not frequently used either. Anyway, and then if you have to monitor, again, depending on what the level is, so our lady was, I think, 112, so she would be a person that you have to monitor her sodium every two hours to see how we're progressing. If you're correcting too fast, and I'm gonna tell you what too fast is in a minute, then you would give her a little bit of D5, because you don't want it to correct too fast. If it's going too slow, then you definitely wanna give more 3%. So that's what this other area here is. There is a use, if you're going too fast, to give decimal pressing. In my experience, we use it, but I always try to do like, the guidelines always say one to two, but I'm telling you, .5 works too. Because sometimes the two last like two, three days, and then you're behind. So anyway, so that's that. So the big risk of treatment of hyponatremia, of course, is osmotic dimelination syndrome, which again, for those that didn't graduate in the last decade, used to be called central pontine myelinosis. And here, where you see the arrows, those are the changes that you would see, here, here, and here, light up. So what are the risk factors? So she has a lot of them. So extremely low serum sodium. The symptoms, like she is already vomiting, she is confused, et cetera, so she has that. She's hypokalemic. Hypokalemia is a risk factor for getting ODS. If alcohol abuse, we don't have a history of that, malnutrition, advanced liver disease, and having a very hypotonic urine are all risk factors for ODS. So those are things. So we wanna correct, but we don't wanna correct too fast that could lead to that. And I'm gonna show you two studies now about the hospital course according to who got or who didn't get ODS. So in this hospital, this was published last year, they had 12 cases of ODS, and the rest, these are other hyponatremia, they did not have ODS. And you can see, obviously, that the ones that got ODS needed help at home when they were discharged compared to the other people. They stayed longer. They were 40 days in the hospital compared to eight in the other people. They also were more likely to die. 37% died compared to 5.3. So again, not good for the patient, not good for the health system. So it's always better to make sure that you're following the guidelines, not overcorrect too fast. And then again, because they are getting ODS, they also used more resources. They were more likely to use desmopressin. They had more CT scans, more MRIs, et cetera. So these are the guidelines. So as some guidelines, some are opinion. So these are the U.S. expert opinion. And they said, and again, they're a little old too because the guidelines are from, this one is from 2012 and the other one's from 2013. So I think it's time to redo them. But this is the guideline right now. So the target is four to eight in a 24-hour period after the patient is admitted, but definitely no more than 10, okay? And then if the person has risk factors for ODS, which I mentioned what they were before, then the target is less because, and that's what the guideline says, and that's the controversy because I'm gonna show you some data where now two investigators have shown that correcting sodium faster is better than slow. And so that's why I was saying that perhaps the guidelines need to be updated. But this is the guideline right now, okay? And then the European guidelines say five, the target of five per 24 hours, limit 10, and this is the same for both. So this is the association of mortality in severe hyponatremia. This study looked at sodiums less than 120. The majority of patients corrected, so 38%, corrected at a rate that was less than six in 24 hours, and they had the highest mortality. So here you can see they looked at it in different models and here in a propensity score, but they did the worst compared to people that had a higher rate, the six to 10, they were the reference. And if you corrected fast, greater than 10, there were less patients there, but they did the best in this study. Again, these are people that showed up like our patient with a sodium of less than 120. This is a different study. This actually was just published last week and basically added all the studies that have been done and comparing very rapid to just rapid, rapid to slow, rapid to very slow, slow to very slow, and you can see that this favors slower correction and this favors faster correction. You can see that every study so far favors faster correction than what the guidelines said. But when we all went to medical school, we were all taught six to eight, no more than 10, et cetera. So I think this is an area of controversy and I think the guidelines have to change because the overwhelming data is that faster is better. Okay, so this is that. Two minutes, please. Oh yeah, I'm almost done. This is our last slide. So here we gave our patient 3% normal saline and you can see that here, this is total cerebral edema. The sulci are not seen, the ventricles are not seen. Then the next day, this is hypothetical, this is not a real patient, right? So they got an MRI and then you can see again the ventricles, you can see the sulci again. So the edema has improved significantly. So hypernatremia, I won't read the summary, you can read it, but I guess my time is up.

hyponatremia

osmotic demyelination syndrome

SIADH

sodium correction

kidney water excretion

treatment guidelines