Transcript
Speaker: Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: And now, your host, Dr. Sergio Zanotti.
Speaker: Disorders of sodium and water balance are common in critically ill patients.
Speaker: Hyponatremia and hypernatremia are associated with increased morbidity and mortality in ICU patients.
Speaker: Although this association may represent a surrogate for underlying severity of disease, there is also a heavy iatrogenic component in their development and the consequences of mismanaging their correction.
Speaker: Today we will discuss this very important topic.
Speaker: Our guest is Dr. Lawrence Weisberg.
Speaker: Dr. Weisberg is the head of the Division of Nephrology and Deputy Chair of Medicine at Cooper University Healthcare.
Speaker: He is a professor of medicine and assistant dean for curriculum at the Cooper Medical School of Rowan University in Camden, New Jersey.
Speaker: Dr. Weisberg is a phenomenal clinician and a medical educator with a long list of publications in the field.
Speaker: It's a true pleasure to have him on the podcast to discuss hypo and hypernatremia.
Speaker: Larry, welcome to Critical Matters.
Speaker: Sergio, thank you so much.
Speaker: It's a pleasure to be here.
Speaker: So I think that when we talk about sodium, most non-nephrologists really think of hyper and hyponatremia, but you probably think more of water balance as opposed to the sodium itself, correct?
Speaker: No, that's exactly right.
Speaker: A lot of people think that the hypo and hypernatremia are disorders of sodium homeostasis, when in fact that's not true.
Speaker: They really are disorders of water homeostasis.
Speaker: And it's important to recognize that.
Speaker: because that's sort of a window into the pathogenesis and pathophysiology of these disorders.
Speaker: And as you point out, these really are common disorders, especially in critically ill patients.
Speaker: We think that hyponatremia, for example, occurs in about 20% of hospitalized patients, but it's up to about 30% of critically ill patients.
Speaker: And even severe hyponatremia,
Speaker: which we can talk about what the definitions of that might be, occurs in maybe 5% to 10% of patients.
Speaker: And we're talking about severe, meaning life-threatening hyponatremia.
Speaker: So yeah, these are fairly common disorders.
Speaker: And I think it's one of those things that people don't think about maybe on a regular basis, but for any of our listeners, guaranteed today in their ICU, there are patients who have
Speaker: disorders of water balance and sodium.
Speaker: And some of those patients might be, like you said, at very high risk of having serious effects from it or from their mismanagement.
Speaker: So I definitely think it's something that we encounter on a daily basis and is worth, I mean, a deeper dive.
Speaker: So why don't we start, Larry, maybe if you could give us like an overview of water homostasis physiology, maybe kind of a basic understanding of what's really happening in the body to start the
Speaker: set the framework for our discussion?
Speaker: Sure.
Speaker: So the first thing I like to think about, though, is why do these disorders matter?
Speaker: Like, who cares about hyponatremia?
Speaker: Why should we care?
Speaker: And if you don't mind, I'll start there because I think it might sort of motivate the rest of the discussion.
Speaker: I'm happy to talk about the underlying physiology and pathophysiology, but the real question is,
Speaker: Why should we even care about these disorders?
Speaker: So let's take hyponatremia, for example.
Speaker: And if you can visualize, I know we don't have any visual aids here, but if you can visualize the brain sort of floating in this sea of extracellular fluid, what happens?
Speaker: And understand that there's an osmotic equilibrium between the brain and its extracellular milieu, right?
Speaker: So water...
Speaker: permeates this semipermeable membrane.
Speaker: And so you achieve osmotic equilibrium between the extracellular fluid and the intracellular fluid of the brain.
Speaker: And what happens when you reduce, for whatever reason, you reduce the extracellular osmolality?
Speaker: What happens is, as you can imagine, water moves down its concentration gradient across the semipermeable membrane
Speaker: into the cells.
Speaker: So from the extracellular fluid space where water now is at a higher concentration, it moves down its concentration gradient into cells and the cells swell, right?
Speaker: Everybody can understand that.
Speaker: Cells swell all over the body.
Speaker: And the reason I'm focusing on the brain is because the brain's swelling is constricted by this rigid calvarium that it sits inside.
Speaker: And so changes in cell volume in the brain
Speaker: get transduced into changes in intracranial pressure.
Speaker: And that's the big problem with hyponatremia, for example, increases in intracranial pressure.
Speaker: And those increases in intracranial pressure are proportional to the magnitude of the hyponatremia that develops and the rapidity with which it develops.
Speaker: And we can talk more about that later.
Speaker: And the converse happens with hypernatremia.
Speaker: So water, again, moves down its concentration.
Speaker: So in this situation, water would move from the intracellular space to the extracellular fluid space, and the brain would shrink.
Speaker: And because it gets some blood supply, for example, from the penetrating vessels from the skull, it could potentially pull away from the skull and rupture those penetrating vessels.
Speaker: blood vessels.
Speaker: That's some concern.
Speaker: Whether it's actually borne out in reality remains to be debated, but that's a significant concern.
Speaker: Okay, so that's why it matters.
Speaker: So it matters because of this brain swelling and shrinking that's associated with changes in extracellular fluid osmolality.
Speaker: And because sodium is the predominant extracellular osmol, changes in sodium concentration are
Speaker: reflected in these changes in osmolality that then have these effects on cell volume.
Speaker: Okay, so that's the setup, right?
Speaker: That's why we care.
Speaker: And hyponatremia, hypo rather than hyper most of the time, hyponatremia is one of really very few potentially lethal electrolyte abnormalities.
Speaker: That's why we worry about it.
Speaker: So, yeah.
Speaker: And just to
Speaker: I think that, and because of these effects that you're describing, Larry, on the brain, I think our colleagues in the neurocritical care world, or in very specialized neurounits, are very keen on sodium because those patients, because of their primary injuries, probably have less of a reserve, and even smaller fluctuations probably can have a tremendous impact.
Speaker: But in common ICUs, people don't see those patients all the time, so maybe we're not as in tuned to the potential dangers, really, of something that's so common.
Speaker: Yeah, I think you're right.
Speaker: I mean, I think patients in neuro-ICUs, because of the underlying neurologic abnormalities, which are often structural, are predisposed to high intracranial pressure anyway, and these disorders would just exacerbate those tendencies.
Speaker: So let's think about
Speaker: normal physiology first, uh, as a way of kind of setting up what the pathophysiology might be that might result in these disorders.
Speaker: So, um, one, one, one sort of thought experiment that I like to do is, uh, uh, imagine what would happen if, I mean, probably several people who are listening to this right now, uh, have, uh, uh, you know, uh, uh, 750 or ML or one liter bottle of water on their desk, uh,
Speaker: what would happen if you drank three of those right now, just drank them down right now?
Speaker: Well, we all know exactly where we would be in probably 10 or 20 minutes.
Speaker: And the question is, why?
Speaker: Why does that happen?
Speaker: Why does it happen that within 10 or 20 minutes of drinking a lot of water, you just have to get rid of that water?
Speaker: So let's follow the
Speaker: Let's follow the sort of the steps involved in that process.
Speaker: So what happens is this water is absorbed from your GI tract, right?
Speaker: You know, when you drink water, it doesn't result in diarrhea.
Speaker: Thank goodness.
Speaker: That water is absorbed from your GI tract and it's absorbed into the extracellular fluid space.
Speaker: And so the osmolality of the extracellular fluid space diminishes just slightly, really very slightly.
Speaker: And that is red,
Speaker: by osmoreceptors.
Speaker: There are, in fact, osmoreceptors in the hypothalamus.
Speaker: These are little specialized cells that sit outside the blood-brain barrier that sense the plasma osmolality and swell or shrink depending on the plasma osmolality.
Speaker: And when they swell or shrink, they send either an inhibitory or a stimulatory signal to other nuclei in the hypothalamus to then
Speaker: either down-regulate or up-regulate a signal, and that signal is antidiuretic hormone, ADH, right?
Speaker: So under conditions where those osmoreceptors swell, they send a negative or an inhibitory signal to these nuclei.
Speaker: They turn off ADH production by the hypothalamus and basically turn off ADH secretion by the posterior pituitary
Speaker: That signal, that circulating ADH signal, is then read by the kidney and specifically by vasopressin to receptors in the collecting duct of the kidney.
Speaker: The collecting duct of the kidney is where urine is concentrated, and it's only concentrated in the presence of vasopressin.
Speaker: Vasopressin acts to insert water channels
Speaker: into the apical membrane of these collecting duct cells so that the filtrate that's flowing through this collecting duct can come into osmotic equilibrium with the very concentrated medullary interstitium of the kidney.
Speaker: So that in the presence of high concentrations of ADH, you have a lot of water channels present in the apical membrane.
Speaker: You can reabsorb a lot of water from the filtrate down its concentration gradient
Speaker: into the medullary interstitium and you put out a maximally concentrated urine that could have an osmolality as high as 1200 milliozins per liter.
Speaker: On the other hand, if you suppress ADH release and there's very low circulating ADH, those receptors are not stimulated, the collecting duct becomes impermeable to water, and you put out a dilute filtrate
Speaker: which could have a urine osmolality as low as 50 milliosms per liter.
Speaker: So the urine can, the urine concentration in milliosms per liter can vary anywhere between 50 in the absence of ADH to as high as 1200 milliosms per liter in the presence of maximum ADH.
Speaker: And it's all in response to the ambient osmolality, right?
Speaker: So that's,
Speaker: So the flip side is, let's say you get dehydrated, and I want to emphasize that term, dehydration.
Speaker: When nephrologists talk about dehydration, they're talking about hyperosmolality, hyperosmolality, not volume depletion, which is different.
Speaker: We look at that differently.
Speaker: I'm talking about dehydration.
Speaker: That is a relative lack of water relative to the amount of solute that's available in the
Speaker: body or in the extracellular fluid.
Speaker: So under conditions of dehydration or hyperosmolality, these osmostats shrink and they send a stimulatory signal to these hypothalamic nuclei that crank out lots of ADH and they create a water permeable collecting duct.
Speaker: So that's the underlying physiology.
Speaker: So then the question is, how could that possibly
Speaker: be disrupted.
Speaker: And the reality is it's not disrupted.
Speaker: And most of us, we hang out with a plasma osmolality that is more or less the same through our entire lives.
Speaker: Most of us have a plasma sodium concentration.
Speaker: You know, normal plasma sodium concentration is 135 to 145.
Speaker: But most of us hang out with sodium concentrations between 138 and 142.
Speaker: for really our whole lives.
Speaker: There's very little fluctuation.
Speaker: And that's because this system that I just described works phenomenally well.
Speaker: Let me also say that there's another component to the hyperosmonality side of this.
Speaker: So that, for example, if you're out in the desert hiking and you forgot to bring a lot of water, well,
Speaker: you're going to get pretty dehydrated pretty fast, and you're going to be at a maximum ADH state.
Speaker: And so you're going to put out a very concentrated urine.
Speaker: You're not going to lose any water through your kidneys.
Speaker: But in order to return your plasma osmolality to normal, you're going to have to drink.
Speaker: And in fact, when your plasma osmolality gets high enough, it stimulates the thirst centers in the hypothalamus to drink.
Speaker: to stimulate you to drink.
Speaker: And you will drink until your plasma osmolality is recovered to normal.
Speaker: So those are the components of the normal osmoregulatory system in the body.
Speaker: So maybe we can jump into hyponatremia first.
Speaker: And maybe just, I mean, you talked a little bit about this at the beginning, but maybe defining it a little bit more precisely and giving us a little bit more of the scope
Speaker: of how often it happens in ICU, and then start talking about how it presents, how you think about it when you encounter it in a consult, and then talk about its management and complications in more detail.
Speaker: Sure.
Speaker: So as I said, it's quite common in the ICU.
Speaker: People, I mean, people who have looked at this have shown that about 30% of patients in the ICU have plasma sodium concentrations less than 135.
Speaker: Uh, so that's quite common, especially given that, uh, what I said just a little while ago, which is that most of us hang out with sodium concentrations that are, you know, 138 or, you know, plus or minus, uh, for our whole life.
Speaker: So, so the fact that, you know, 30% of people in the ICU have sodium concentrations well below that, uh, tells you that it's quite a common disorder in that situation.
Speaker: Um, so, uh,
Speaker: So when I have a patient with hyponatremia, what I like to think about is how could this possibly have happened, given how beautiful and elegant the protective mechanisms are against the development of hyponatremia.
Speaker: So generally speaking,
Speaker: In order to get a sodium concentration less than 135, you have to somehow take in more water than you get rid of.
Speaker: So the question is, is it possible to take in so much water that you could overwhelm the normal diluting capacity of the kidney?
Speaker: And the answer is yes, it is possible.
Speaker: I mean, the estimates are that somebody with normal diluting capacity with an intact diluting system the way I just described it, that person would have to drink anywhere between 18 and, say, 24 liters of water a day in order to exceed their normal diluting capacity.
Speaker: So that's really a pretty deceit.
Speaker: I mean, that becomes a full-time job, basically.
Speaker: So most people can't do that.
Speaker: But there are some folks who are really motivated, who are just absolutely determined to drink a tremendous amount of water in a very short time.
Speaker: And those people can overwhelm their diluting capacity and develop sometimes really profound hyponatremia.
Speaker: We call that problem primary polydipsia.
Speaker: In the past, we used to call it psychogenic polydipsia.
Speaker: or compulsive water drinking.
Speaker: And now we use a less pejorative term, and we just call it primary polydipsia.
Speaker: And the estimates of how much water you can drink and get rid of depends somewhat on the rapidity with which you drink that water, the rate at which you drink that water.
Speaker: But it also depends on how much solute, how much fixed solute you have to get rid of through your kidneys every day.
Speaker: I don't want to go into a lot of detail on this, but basically the amount of water that you can get rid of in a day, because you can't get rid of pure water, the lowest osmolality you can achieve in the urine is about 50 milliozms per liter, as I said.
Speaker: That means that you have to have a certain amount of solute in which that
Speaker: to dissolve in that water that you're going to get rid of is urine.
Speaker: If you don't take in very much food, let's say, that generates fixed solute that you have to get rid of through the kidney, and that's in the form of either urea or electrolyte or some combination thereof, if you don't take in a lot of protein and take in some electrolyte that you have to get rid of, you can't get rid of that water.
Speaker: or you can't get rid of as much of that water as you might if you took in more solute-generating stuff.
Speaker: So there are folks who take in a lot of water and very little solute that they have to get rid of.
Speaker: And those people, classically, are really enthusiastic beer drinkers.
Speaker: So there are people who drink liters and liters of beer a day,
Speaker: And because they get all their calories in the form of carbohydrate, which generates nothing but CO2 and water and very little fixed solute, they can't get rid of that water that they take in.
Speaker: And they retain that water and therefore they develop hyponatremia.
Speaker: So there is this beer drinker podomania, as it's been called, podomania, meaning a mania for drinking.
Speaker: So the
Speaker: That's a unique situation.
Speaker: We see it in other circumstances or that mechanism kick in in other circumstances, but that's the idea behind it.
Speaker: So anyway, so because it's possible to do this, to take in so much water over a short period of time that you just can't get rid of, the first thing that I do when I'm evaluating a patient with hyponatremia is to look at their uranosmolality.
Speaker: If their uranosmolality is super low, meaning...
Speaker: 50-ish, or let's say just less than 100, then that's a person who I would suspect has primary polydipsia or buropodomania.
Speaker: But we see that in about, I don't know, I'm guessing here, less than, certainly less than 5% of patients in whom were consulted for hyponatremia.
Speaker: Most of the time what we see is a concentrated urine.
Speaker: We see somebody who has
Speaker: low plasma osmolality and has a concentrated urine.
Speaker: So you might say, well, that's completely crazy.
Speaker: How could that possibly happen?
Speaker: And the answer is that you have to look at the... So what the high urine osmolality implies and almost always equates to is a high circulating plasma ADH concentration.
Speaker: So you might say, well, that's crazy.
Speaker: How can you have a high circulating plasma ADH concentration when you have a low plasma osmolality that's supposed to suppress ADH release by the brain?
Speaker: And the answer is that there is another physiologic stimulus for ADH release besides osmoregulation.
Speaker: And that is...
Speaker: a hemodynamic or baroreceptor mechanism for the stimulation of ADH.
Speaker: Remember, the other name for ADH is vasopressin, arginine vasopressin, and they don't call it vasopressin for nothing because it actually has V1 receptor activity, and that is vasoconstrictive.
Speaker: So vasopressin is a vasoconstrictor, and it is
Speaker: released under conditions of low blood pressure or low stretch of baroreceptors, which can occur in severe volume depletion as well.
Speaker: So if I see a patient who has hyponatremia and has a concentrated urine, then the next step for me is to look at the patient's volume status and their hemodynamics.
Speaker: and try to see whether they have a volume stimulus or a baroreceptor stimulus for their high ADH.
Speaker: And that's really based on their physical examination.
Speaker: If I have other tools at my disposal, like, you know, maybe they have a central line and I can measure their central venous pressure or I have some other tools at my disposal, or I'll tell you one little nephrologist tool, and that is the
Speaker: the urinary sodium concentration.
Speaker: If the urinary sodium concentration is very low in this situation, then that's consistent with some stimulus for the kidney to avidly reabsorb sodium along the nephron.
Speaker: And that's typically associated with volume depletion or hypotension.
Speaker: So that's an added piece of information that would tell me, yeah, this person is
Speaker: may have a baroreceptor mechanism for their high ADH state.
Speaker: So if at that point I make that decision, I make that judgment that the patient has a baroreceptor mechanism, then that's a perfectly valid explanation for their water retention under that circumstance.
Speaker: Does that make sense?
Speaker: Yep.
Speaker: And how do you, so what would you regularly get?
Speaker: I mean, a lot of times, I guess, you've seen these patterns over and over again, and there's also probably combinations.
Speaker: Do you always get a set of tests or sometimes, I mean, based on what you have available, you can figure out what you need?
Speaker: Is there anything else that you would order in the diagnostic approach?
Speaker: Sure.
Speaker: So, yeah, that's a great question.
Speaker: So the first things that I would order, um,
Speaker: if it's a patient who's coming in from outside the hospital and they have hyponatremia, then undoubtedly they have hypotonic or hypoosmolar hyponatremia.
Speaker: There are conditions under which you can see hyponatremia where it's not associated with hypoosmolality, where it's actually associated with hyperosmolality, actually even in patients coming in from outside.
Speaker: And that is where they have a
Speaker: a non-sodium solute in the extracellular fluid that's causing water movement out of cells into the extracellular fluid space and diluting the sodium that's in the extracellular fluid space.
Speaker: And the example that I'm sure you're thinking of right now is hyperglycemia.
Speaker: So patients who are very hyperglycemic have a reduction in their plasma-sodium concentration just because of water movement out of cells to dilute that
Speaker: as a result of the hyperglycemia.
Speaker: That's hypertonic or hyperosmolar hyponatremia.
Speaker: We don't really worry about that because it's not associated with cell swelling.
Speaker: It's associated with cell shrinkage.
Speaker: So we don't worry about the hyponatremia per se.
Speaker: In hospitalized patients, sometimes they're given a solute like that specifically to
Speaker: cause brain shrinkage.
Speaker: And the one that I'm thinking about is mannitol.
Speaker: Sometimes they're giving glycerol as well.
Speaker: And those can do the same thing as glucose.
Speaker: And that is cause water movement out of cells, dilute the sodium in the extracellular fluid space and cause hyponatremia with hyperosmolality.
Speaker: Again, we don't care about the hyponatremia, but, but because you don't measure mannitol or glycerol on a chem seven, um,
Speaker: or a basic chemistry panel, it makes sense in that situation, if there's any concern about that, to measure the plasma osmolality.
Speaker: So the first step in evaluating a patient with hyponatremia might be to measure the plasma osmolality and just reassure yourself that it is, in fact, hyposmolar hyponatremia.
Speaker: Once you do that, the next step is to look at the urine osmolality.
Speaker: As I said, if the uranosomal is really low, then it's primary polydipsia or something like buropodomania.
Speaker: If it's not low, if it's anything but low, meaning anything over 100, then they're in a high ADH state almost certainly, and we'll talk about some possible exceptions, but almost certainly in a high ADH state.
Speaker: And the next step along the way is to try to assess their plasma volume, the extracellular fluid volume and hemodynamics,
Speaker: as I just mentioned.
Speaker: And one of the useful things there is the urine sodium concentration.
Speaker: Sometimes the sodium is not so helpful and you would want to urine chloride as well.
Speaker: And the potassium can also be helpful in the urine for reasons that I'll tell you about in a minute.
Speaker: And so you would check the urinal electrolytes, all the urinal electrolytes.
Speaker: So that's really
Speaker: Those are all the sort of fancy chemicals at this point, right?
Speaker: Just a plasma osmolality, urine osmolality, and urinal electrolytes.
Speaker: And you can get those all at once.
Speaker: That would be very helpful.
Speaker: Typically, what we see is that there's a delay in the ordering and the return of those labs, those very basic and essential labs in our evaluation, until after there's been some intervention made.
Speaker: And that just really muddies the picture for us.
Speaker: So the great thing is to see a patient with hyponatremia and just whammo, get all those studies right off the bat.
Speaker: That would be extremely helpful.
Speaker: So just to recap, what would be the studies that you would get in these patients so that the audience, I mean, can really focus on this?
Speaker: Plasma?
Speaker: Yeah, plasma osmolality, uranosmolality, and urine electrolytes.
Speaker: Okay.
Speaker: Okay.
Speaker: Like you said, I mean, that's pretty easy.
Speaker: And we have a lot of our, a lot of colleagues from the ED who listen to this and they're the ones a lot of times who have the opportunity to get it up front and can really help us in terms of figuring out which directions we need, we need to go.
Speaker: Excellent.
Speaker: Exactly.
Speaker: Yeah, exactly.
Speaker: Yep.
Speaker: Um, so, so I was just walking through this a little bit further and, and, um, stop me if you, if you have any questions, but, but, um,
Speaker: So let's say you have a patient who has true hypotonic hyponatremia.
Speaker: They have a high uranosolality, which is what we see in 95% of the patients in that situation.
Speaker: You assess their volume status and you say, no, this patient's not volume depleted.
Speaker: And in fact, when you measure their urinal electrolytes, they have a lot of electrolyte in there.
Speaker: Say their sodium and potassium concentration is quite high.
Speaker: Let's say it adds up to 100 or more.
Speaker: milliequivalents per liter, that's a patient who seems neither to have a baroreceptor mechanism for their high ADH state nor an osmoreceptor stimulation for their high ADH state.
Speaker: That is a person who would then fall into the category, possibly, of somebody who has SIADH.
Speaker: And that I, that inappropriate, means inappropriate for both
Speaker: the physiologic regulators of ADH, the Osmo regulation and the Barrow regulation.
Speaker: So that's what that I names, inappropriate for both the physiologic regulators of ADH.
Speaker: And then, so then we walk down the path of SIDH.
Speaker: But in order to get to the path of SIDH, you have to jump over two hurdles.
Speaker: And those two hurdles are two endocrine abnormalities that could potentially result
Speaker: in an ADH-independent urinary concentration.
Speaker: And those two endocrine disorders are hypothyroidism and adrenal insufficiency.
Speaker: So both of these, we think, can be associated with urinary concentration even in the absence of ADH.
Speaker: The data there are a little murky, but both of those
Speaker: endocrine abnormalities can be associated with hyponatremia, and so it's useful to look for those anyway.
Speaker: And one of the advantages in critically ill patients is that a spot cortisol can rule it out, right?
Speaker: So, I mean, if you have a spot cortisol and somebody who's critically ill that's above 25, it's very unlikely that they're truly adrenal insufficient.
Speaker: And...
Speaker: In a hospitalized patient or somebody who's not critically ill, obviously there's a circadian rhythm, it might be more difficult, but at least in a lot of the patients that we see in the ICU, you can kind of at least rule that out very quickly.
Speaker: And with thyroid, I mean, getting the thyroid hormone test, you can figure that out as well.
Speaker: Right, right.
Speaker: So one of the, yeah, go ahead.
Speaker: So I think just to emphasize, one of the big differentiators obviously is in those people who don't have any reason to have a high ADH is when we think about SIADH.
Speaker: But one of the things that I've also seen a lot in the critical care world is differentiation, especially in neuro patients, between SIADH and salt wasting, which is
Speaker: Some believe it exists and some don't believe it.
Speaker: I don't know if this is the right time to talk about that, but volume status has always been something that people bring up on a clinical side as something that you want to evaluate because if you're not euvolemic, it's probably not SIDH, correct?
Speaker: Oh, that's right.
Speaker: Yeah.
Speaker: Patients with SIDH typically are subtly volume expanded because they are hanging on to water.
Speaker: And so they're a little bit volume expanded.
Speaker: They have copious electrolyte in the urine.
Speaker: People in whom people would entertain the diagnosis of cerebral salt wasting, those folks typically look volume depleted.
Speaker: But the problem is, you know, I said that the urine electrolyte concentration is
Speaker: under most circumstances, a pretty good window into a patient's volume status because if they're volume depleted, they tend to be in a sodium avid state, sodium chloride avid state.
Speaker: They tend to have very low urinary sodium and chloride concentration.
Speaker: But in these folks who are postulated to have cerebral salt wasting, they can be volume depleted and have lots of sodium in the urine.
Speaker: And that's thought to be the primary mechanism for their volume depletion is that there's salt wasting.
Speaker: So it can be really confusing.
Speaker: And to add to the confusion, and this is really crazy, those people, typically people who get volume depleted, have very high serum uric acid levels because of the reabsorption of uric acid along the nephron under states of volume contraction.
Speaker: The people with cerebral salt wasting tend to actually have low serum uric acid concentrations because they seem to waste uric acid as well.
Speaker: I don't know if that's the right term, to waste uric acid, because uric acid is a waste product, but they tend to have high urinary excretion of uric acid for reasons that are thought to be primary to the disturbance.
Speaker: So it's super confusing to try to understand how to discriminate between the cerebral salt wasting and SIDH.
Speaker: Both are characterized by hyponatremia with a lot of electrolyte in the urine and low serum uric acid levels.
Speaker: So it can be really confusing.
Speaker: And the only discriminating feature really is what happens to them when you restrict their sodium intake.
Speaker: If you restrict the sodium intake of somebody with SIDH, well, eventually they'll come into sodium balance.
Speaker: They will eventually reduce their urinary sodium concentration to something low, showing that the kidney can respond to the normal physiologic mechanisms that come into play with volume depletion.
Speaker: But somebody with cerebral salt wasting will never reduce their urinary sodium concentration, and they will continue to
Speaker: have a naturesis into a state of volume contraction, I mean, obvious volume contraction.
Speaker: So that's the discriminator.
Speaker: The question is, how do you decide when somebody's volume contracted?
Speaker: And I think that's what you were getting at before.
Speaker: It's often not easy.
Speaker: I mean, we don't have great ways of assessing people's volume status.
Speaker: So it can be quite confusing.
Speaker: In terms of treatment, Larry, I guess that if somebody who has severe symptoms, and we can talk about what those would be, the treatment is the same regardless of the cause, right?
Speaker: And once you get a patient into a safe zone, it's really about kind of refining and maybe changing your approach based on what you think is going on.
Speaker: Would that be fair?
Speaker: That's exactly right.
Speaker: That is exactly right.
Speaker: So we treat severe symptomatic hyponatremia
Speaker: the same way regardless of what we think the cause might be.
Speaker: And that is to give hypertonic saline.
Speaker: That's the treatment for acute, or not necessarily acute, but severe symptomatic hyponatremia.
Speaker: So your question is, what do we mean by that?
Speaker: What's symptomatic?
Speaker: And the answer is the symptoms really can range from
Speaker: sort of anorexia, nausea, when the sodium is like, you know, between 120 and 125, let's say people can feel a little anorexic, a little malaise, you know, maybe a little confusion, progressing to real encephalopathy, coma, seizures, and even death, right?
Speaker: So,
Speaker: And the severity of the symptoms tend to correlate fairly well with the severity of the hyponatremia.
Speaker: But people who have longstanding, like really chronic hyponatremia tend to tolerate their hyponatremia way better than people who develop really acute hyponatremia.
Speaker: And we can talk about who those folks are.
Speaker: But when anybody shows up with any symptoms
Speaker: signs or symptoms that might be construed as being due to cerebral edema, we treat those people as if they have severe hyponatremia.
Speaker: And one of the things that I see commonly, and maybe you can tell us first how you would treat it specifically, but I see that often people use normal saline to correct hyponatremia, and that never seems to take us where we want to go.
Speaker: Well, that's a great way to put it.
Speaker: It depends on what the cause of the hyponatremia is.
Speaker: If you have a patient who is hyponatremic because they are volume depleted, let's say it's somebody who, for example, had bad diarrhea.
Speaker: They came back from Thailand where they were eating terrific street food and ended up with this terrible traveler's diarrhea.
Speaker: And their idea of compensating for that was just to drink a lot of water.
Speaker: So they got volume depleted because of all the electrolyte loss.
Speaker: And they were replacing all that just with water.
Speaker: They couldn't get rid of the water because they were in a high ADHD state because it got volume depleted.
Speaker: And they come in hyponatremic, right?
Speaker: So what is the treatment for that patient?
Speaker: The treatment for that, so that patient, just to be clear, would have a concentrated urine.
Speaker: They would have a high urinal osmolality, but they would have very low urine electrolyte concentrations.
Speaker: right?
Speaker: Because they're volume depleted.
Speaker: The treatment for that patient could very well be normal saline, could very well be normal saline, just to volume expand them and turn off the baroreceptor stimulus for ADH.
Speaker: And immediately they'd be able to dump out that water.
Speaker: So the normal saline in that situation would work perfectly well, perfectly well.
Speaker: So in, in,
Speaker: so to be really clear in that situation, the tip off is the, is the low urine electrolyte concentration.
Speaker: That's a patient who is, who may very well, not won't necessarily, but may very well respond just to normal saline administration.
Speaker: Uh, a patient with SIDH on the other hand, uh, is very unlikely to respond to normal saline alone, um, uh, to bring up their sodium concentration.
Speaker: Um,
Speaker: Because there, they don't have a baroreceptor mechanism for their ADH.
Speaker: It's inappropriate ADH even to their baroreceptor mechanism.
Speaker: And so just giving them volume in the form of crystalloid is not going to turn off their ADH.
Speaker: And in fact, there are some people with SIDH whose diluting defect is so bad that giving them normal saline
Speaker: may actually worsen their hyponatremia.
Speaker: And the reason, and the tip-off in those folks is, if they have a urine electrolyte concentration that is greater than the electrolyte concentration in normal saline, and you can see that in some of these folks with bad SIDH, if their electrolyte concentration in the urine is higher than the electrolyte concentration in normal saline, they are what we call desalinators.
Speaker: They will take that normal saline and they will
Speaker: put out hypertonic saline and reabsorb the water from the saline solution that you give them, and it'll drive their sodium lower.
Speaker: So you have to be really careful about whom you give normal saline to in this situation.
Speaker: And in an emergency situation where we have defined severe symptoms as CNS and symptomatology, how would you treat that patient, Larry, in terms of as an emergency?
Speaker: Yeah.
Speaker: So the current recommendation is to give enough hypertonic saline to raise their plasma sodium concentration by six milliequivalents per liter in six hours and then stop.
Speaker: That's it.
Speaker: Because there's a lot of concern about overcorrection.
Speaker: So how do we give enough...
Speaker: 3% saline, in order to do that, it's really trial and error.
Speaker: The recommendation these days is to give a bolus of 100 mLs of 3% saline and then recheck the plasma sodium a while later, let's say an hour later.
Speaker: There'll be plenty of time for re-equilibration.
Speaker: So give 100 mLs of 3% saline as a bolus over 10 minutes and
Speaker: and then recheck the plasma sodium.
Speaker: If it's not where you want, then you can give another 100 mLs and recheck.
Speaker: And your target is an increase of 6 mEq per liter.
Speaker: So if the patient comes in and they have a plasma sodium concentration of 110 mEq per liter, your target is to raise their plasma sodium to 116 and then stop.
Speaker: Don't give them any more 3% saline increase.
Speaker: for the next 24 hours, really just leave them where they are.
Speaker: And the rationale behind this is the recognition that just that small amount of change in their plasma osmolality will ameliorate the cerebral edema.
Speaker: And, yeah.
Speaker: And I think that, so that's an important point, right?
Speaker: You just want to make a small change up front
Speaker: And that will be enough to prevent the patient from dying from the consequences of cerebral edema, number one.
Speaker: But number two, and you mentioned this a little bit more, but I want to dive deeper in, what are the dangers of overcorrection and what should be our target after we've accomplished our move with the bolus of hypertonic saline?
Speaker: Yeah, so overcorrection, there's been a huge amount of debate over this for the last
Speaker: 30 years, really 30 years, what constitutes overcorrection.
Speaker: And by overcorrection, I mean too rapid correction.
Speaker: I don't mean overshoot, but that can happen too.
Speaker: But I just mean correction that's too rapid.
Speaker: And so I'm just going to give you the bottom line after 30 years of debate about this.
Speaker: The bottom line is
Speaker: that the maximum rate of correction for somebody with severe hyponatremia is no more than 10 milliequivalents in the first 24 hours.
Speaker: Some people would say eight, some people would say 12, but let's just round it off and say 10 milliequivalents per liter in the first 24 hours.
Speaker: Nobody should be corrected more rapidly than that.
Speaker: And the question is why?
Speaker: And the answer is because more rapid correction than that is associated with really catastrophic, can be associated with catastrophic neurologic consequences.
Speaker: And they fall into the category or under the diagnosis of the osmotic demyelination syndrome, ODS.
Speaker: We used to call this central pontine myelinolysis,
Speaker: because that was where it was first recognized to occur, but now we know that it can be much more diffuse lesion than that.
Speaker: And so we call it the osmotic demyelination syndrome.
Speaker: And so what does this syndrome look like?
Speaker: It presents typically as motor abnormalities, often involving speech, but other motor abnormalities as well.
Speaker: Sometimes cognitive impairment,
Speaker: And it doesn't show up typically, and this is the sort of really bothersome thing about it.
Speaker: It doesn't show up for anywhere between three and 10 days after the correction of the sodium.
Speaker: So just because the patient the next day looks fine doesn't mean you're out of the woods.
Speaker: And there are certain populations who are predisposed to this, and people should recognize this.
Speaker: So you want to be extra careful in the very young, so kids, the very old.
Speaker: Women, for some reason, are at greater risk than men.
Speaker: People who are malnourished, chronically malnourished.
Speaker: People who are hypokalemic, as well as hyponatremic.
Speaker: And people with a history of alcohol ingestion.
Speaker: Those are the folks who are at most risk of this osmotic demyelination syndrome.
Speaker: Is it reasonable to assume that if you have a very high risk patient, that maybe even a lower target for 24 hours would be in place?
Speaker: I would say, yes.
Speaker: Yes, I think that's right.
Speaker: And the reason that that's right is because the biggest risk in the treatment of hyponatremia is overcorrection.
Speaker: We tend to overcorrect.
Speaker: Yeah.
Speaker: There's a fair amount of literature on this, mostly coming out of a group in Rochester, New York, showing that most patients get overcorrected.
Speaker: And so I think in these high-risk folks, you should target a lower rate of correction.
Speaker: Yeah, I think that would be totally sensible.
Speaker: And let me clarify a question.
Speaker: When you say that, so let's assume that the target, like you said, is for most patients is overcorrected.
Speaker: a delta or a change of 10 mil equivalents in 24 hours.
Speaker: What happens, and this might not be the best example, but what happens if I start very aggressively, totally overshoot, go over 10, and then I do things to bring it down, and at 24 hours, I'm below 10.
Speaker: Is the damage done at that point?
Speaker: I'll tell you that we don't really have any data in human beings about this.
Speaker: We don't know.
Speaker: So in other words, if you overcorrected and then an hour or so or two hours, three hours later, you back it down, have you mitigated the damage?
Speaker: And the answer is nobody really knows.
Speaker: There's some animal data to show that backing it down is beneficial, but we don't have any human data.
Speaker: And so based on that, based on the really sometimes catastrophic osmotic demyelination syndrome, and I should emphasize that that syndrome can actually result in permanent neurologic deficits.
Speaker: That's the real concern.
Speaker: So because that's such a concern, I think it's reasonable to, you know, to try to do this backing down if you've overcorrected.
Speaker: And the way you can back down is just by giving water, but it's not just enough to give water usually at that stage because most of the time where we see this is in folks who come in like my person from Thailand with the diarrhea and the hyponatremia on a baroreceptor mechanism.
Speaker: What's happened is you've suppressed their, you've suppressed their ADH by volume expanding them.
Speaker: And so now if you give them water,
Speaker: they'll just get rid of the water, right?
Speaker: So at that point, what you have to do is give them water and some vasopressin to get them to hang onto the water and back them down that way.
Speaker: It seems paradoxical and maybe overly fussy, but I think given what we recognize as the potential risk, it makes sense to do that.
Speaker: And I think this is an important point, Larry, because I do believe that fortunately,
Speaker: especially most young clinicians have not seen one of these cases.
Speaker: So I think that sometimes people tend to think, well, this doesn't make any sense.
Speaker: It's like giving Lasix and fluid, right?
Speaker: I mean, at the same time almost.
Speaker: But I think that because of the potential danger and when it happens, it can be devastating, not only permanent damage, but even lead to death.
Speaker: I think that it definitely merits that type of caution, right?
Speaker: Yes, I couldn't have said it better, and I didn't say it better.
Speaker: So I think that from what I'm hearing, there's really three things that people need to keep in mind when they're correcting sodium to avoid causing permanent and irreversible hyphrogenic damage from the osmotic demyelination syndrome.
Speaker: Number one is, if somebody has severe symptoms, use small boluses of
Speaker: hypertonic saline.
Speaker: So don't put them on a drip.
Speaker: Just give them 100 cc's, mLs over 10 minutes.
Speaker: Recheck the sodium.
Speaker: See where you are.
Speaker: If needed, give them another 100.
Speaker: Now, probably 300 mLs is probably the limit if you want to increase by 6, right?
Speaker: If you're giving your 6 bolus, probably something's wrong.
Speaker: Yeah, that ought to do it.
Speaker: I mean, that ought to do it in most people.
Speaker: It depends on the size of the individual, but yeah, in most folks, that ought to do it.
Speaker: And so the first point is boluses, small boluses of hypertonic saline.
Speaker: The second point is frequent sodium checks.
Speaker: So not only you know where you are, but you can anticipate what's going on.
Speaker: And what would you recommend in terms of the frequency?
Speaker: Well, it has to be individualized.
Speaker: But I would say in these folks, the changes can happen fairly quickly, especially in people who have, and I want to
Speaker: I want to highlight these people as a special group, the people with the baroreceptor mechanism.
Speaker: All you do is you dial back their physiology by volume expanding them and whammo, they get rid of a lot of water really fast.
Speaker: And so really those folks, you need to be checking them every probably four hours.
Speaker: That would be a reasonable thing to do.
Speaker: And the last thing I was going to say is, which I think is important,
Speaker: but I think our nephrology colleagues are very, very aware of this, but I think a lot of times in the critical care world, we're not as aggressive with correcting our overcorrection.
Speaker: So if we go over to really try to bring back as soon as possible that sodium so that it falls within that safe range that we mentioned of the maximum of 10 milliequivalents change in 24 hours.
Speaker: Yes, yes.
Speaker: Now I will, I want to just put a,
Speaker: a plug-in for a special group of patients.
Speaker: And the special group of patients is folks who develop acute, acute severe hyponatremia.
Speaker: And there are two special groups I want to talk about.
Speaker: One is postoperative patients, and especially postoperative young women.
Speaker: For some reason, these folks are at particular risk for developing severe acute hyponatremia postoperatively.
Speaker: if they're given hypotonic fluids in that period.
Speaker: So they can drop their sodium from normal to 115 in a couple of hours.
Speaker: Those people are at extremely high risk of catastrophic cerebral edema.
Speaker: Those people, you want to get them back to 140 as quickly as they got from 140 to 115.
Speaker: You can take them right back up immediately.
Speaker: without any deleterious consequence.
Speaker: And in fact, if you delay the treatment of them, they really can get into serious trouble.
Speaker: And just to point out to our colleagues, these are usually healthy women who might be getting laparoscopic type surgeries.
Speaker: So they're not necessarily critically ill women, right?
Speaker: So we might be called to see them as intensivists, but these are usually people who came to the hospital relatively healthy or not at least considered critically ill, right?
Speaker: That is exactly right.
Speaker: These are young, otherwise completely healthy women.
Speaker: And for some reason, they're predisposed to hang on to this water that they get around the time of the surgery.
Speaker: And there are too many cases in the literature of catastrophic outcomes in this population because there was delayed recognition and delayed treatment.
Speaker: And the treatment is get their sodium back up as quickly as possible with hypertonic saline.
Speaker: Okay.
Speaker: And the other group, interestingly enough, is also a healthy population, and that is marathoners.
Speaker: Marathoners who drink, you know, who basically stop at every water station.
Speaker: Those folks can have serious symptomatic hyponatremia at the end of the race.
Speaker: And those people also, because they develop their hyponatremia so quickly, need to be brought up just as quickly as they came down.
Speaker: none of this six in six hours and stop.
Speaker: You get them back to normal.
Speaker: So if any of the folks who are listening are attending in the tents at the end of a marathon, you'll know exactly what to do.
Speaker: Get those people back up really quickly.
Speaker: Excellent.
Speaker: So I think that...
Speaker: Any other comments you want to make specifically about treating other specific causes of hyponatremia?
Speaker: So we said that acutely we know what the goal is, is to get them out of the danger zone, prevent overcorrection.
Speaker: Any particular specifics for patients, let's say, after 24 hours or 48 hours?
Speaker: Larry?
Speaker: Well, you know, after that period of time, it really depends on what the cause of their hyponatremia was.
Speaker: If the patient has SIDH, then just typically just water restriction alone is not going to be very effective in maintaining a normal serum sodium, and they may need some adjunctive therapy.
Speaker: And there are a couple of interesting adjunctive therapies, but I'm not sure they really
Speaker: would be terribly fascinating to a critical care audience.
Speaker: Unless you think... Well, I think that they're more long-term, so I'll put some references in the show notes.
Speaker: And I mean, we're talking about like V2 receptor antagonist and other things of that nature, which really we never prescribe in the ICU.
Speaker: That's right.
Speaker: That's right.
Speaker: V2 receptor antagonist and also these days oral urea,
Speaker: oral urea to increase the non-electrolyte solute in the urine and increase their urinary electrolyte-free water excretion.
Speaker: But that's a non-ICU kind of therapy.
Speaker: So I always feel bad for hypernatremia because in every chapter that I read, there's like several pages on hyponatremia and there's like a blurb on hypernatremia.
Speaker: It seems that the podcast is going to be the same.
Speaker: But why don't we pivot to hypernatremia
Speaker: and start by defining it.
Speaker: What are the clinical manifestations and maybe how you would approach it in the ICU?
Speaker: Sure.
Speaker: So the hypernatremia is easily defined.
Speaker: I mean, it's a sodium greater than 145.
Speaker: And the thing to recognize about hypernatremia is we have good defenses against hypernatremia in the form of ADH, right, that allows us to hang on to water and
Speaker: the thirst mechanism that I talked about earlier.
Speaker: That is, you know, when our plasma osmolality gets up to about 292 from normal 285, our thirst center gets stimulated and we are desperate to get hold of some water and drink that water.
Speaker: So it's obvious to wonder then, how can anybody get hypernatremic?
Speaker: And the answer is,
Speaker: it almost always occurs in people who either don't have access to water or don't have an intact thirst mechanism.
Speaker: And those people mostly are elderly, debilitated folks, usually neurologically debilitated, who either don't have an intact thirst mechanism or they can't express their thirst or they don't have access to water, can't get access to water.
Speaker: And some people have called hypernatremia
Speaker: any atrogenic disturbance because it's something that we ought to be able to recognize quickly and be able to intervene on quickly.
Speaker: And the intervention really is almost always just giving enough electrolyte-free water to replace the electrolyte losses that the patient has.
Speaker: So, sorry, the water losses that the patient has.
Speaker: So when we think about patients with hypernatremia, we think about how they might have gotten there.
Speaker: So we can understand that the reason that they are maintained in their hypernatremia is because they don't have access to water, but how did they get there in the first place?
Speaker: And there are really three ways that they can get there.
Speaker: One is common, and the other two are uncommon.
Speaker: The common way is to lose salt and water
Speaker: but water in excess of salt.
Speaker: And that usually happens because of GI losses or urinary losses.
Speaker: So for example, if a patient's on a diuretic medication, they lose water in excess of salt.
Speaker: And so if there's no intervention made, they will get progressively hypernatremic.
Speaker: If they lose GI fluids, either diarrhea or upper GI fluids, and those losses are not replaced,
Speaker: they will lose water in excess of electrolyte and get progressively hypernatremic.
Speaker: Those people look volume depleted.
Speaker: They look volume depleted because of the electrolyte loss.
Speaker: And so what those folks need is to have electrolyte containing solutions to replace their volume loss and get them to be euvolemic and then address their water losses.
Speaker: their water deficit, which can be calculated using a formula that anybody can have access to, and replace any ongoing water losses that they have.
Speaker: So that's the sort of basic approach to the patient with volume depletion associated with hypernatremia.
Speaker: There are some folks, fairly uncommonly, who lose weight
Speaker: essentially pure water.
Speaker: And the sort of paradigm of that is diabetes insipidus, either central DI or nephrogenic DI.
Speaker: Those people lose essentially pure water.
Speaker: And so they tend to look euvolemic.
Speaker: And the reason they look euvolemic is because they have lost electrolyte.
Speaker: And water, if they're just losing pure water, water can be lost from
Speaker: is lost from all body water compartments, including the intracellular space.
Speaker: And so they can get pretty hypernatremic and have very little extracellular or intravascular volume loss.
Speaker: Does that make sense?
Speaker: Yep.
Speaker: And I think that DI is not something that we see very commonly in general ICUs.
Speaker: I think, again, it's something that we see much more in people who have
Speaker: significant brain damage or certain types of neurosurgeries, they're very sensitive about the eye because they can expect it almost.
Speaker: But I do think it's worth talking a little bit more about it, Larry, because the one situation where I've seen clinicians get confused and mismanage this is in non-specialized, so non-neural ICUs in patients who become brain death and are becoming organ donors.
Speaker: These are patients who obviously on one hand
Speaker: are dead, but we are trying to preserve the organs for donation, and these patients commonly will develop DI.
Speaker: And some people just don't get it that the point of treating these patients DI is to maximize the potential usefulness of these organs.
Speaker: Could you talk a little bit more about how you would treat or recognize these patients?
Speaker: Sure.
Speaker: So the way that diabetes insipidus typically shows up is with polyuria,
Speaker: So polyuria associated with hypernatremia.
Speaker: And the worry is, and we get called not uncommonly for that exact situation, the worry is diabetes insipidus.
Speaker: So the question is, is there a differential diagnosis for polyuria and hypernatremia?
Speaker: And the answer is, yes, there is a differential diagnosis.
Speaker: And the differential diagnosis includes
Speaker: polyuria because of a non-electrolyte osmotic diuresis versus a water diuresis like diabetes insipidus.
Speaker: So what do I mean by a non-electrolyte osmotic diuresis?
Speaker: What I mean is, and the obvious one here is, somebody who's extremely hyperglycemic.
Speaker: Hyperglycemia.
Speaker: Hyperglycemia will drive an osmotic diuresis.
Speaker: but they're losing a ton of glucose-containing water in the osmotic diuresis, and that is depleting them of electrolyte-free water, and they're getting hypernatremic on that basis.
Speaker: The other situation that we see, not in your organ donor, but we see it not uncommonly in the ICU, is a patient who's on parenteral nutrition and getting very high amino acid infusions, and they generate a tremendous amount of urea,
Speaker: And they have to get rid of that urea through the kidney.
Speaker: So that generates a non-electrolyte osmotic diuresis.
Speaker: And they become hypernatremic.
Speaker: So when we see a polyuretic patient with hypernatremia, the first thing we do is we look to see what's in that urine.
Speaker: Is it mostly water or is it mostly solute?
Speaker: And so we check the osmolality of that urine that's coming out, that copious urine.
Speaker: If it's got a urine osmolality that is isotonic or higher, meaning same as plasma or higher, then we say this is an osmotic diuresis.
Speaker: And then the question is, what's the osmo?
Speaker: Is it electrolyte or non-electrolyte?
Speaker: And so we send the urine for electrolytes.
Speaker: And if it's got a high electrolyte concentration, if the electrolytes make up more than half of the osms, then we say this is an electrolyte diuresis.
Speaker: This is somebody who
Speaker: had, let's say, gotten a lot of electrolyte previously in the form of crystalloid fluids and is now dumping them or has ongoing electrolyte administration.
Speaker: On the other hand, if the patient has, if most of their solute is not electrolyte, then that's a non-electrolyte osmotic diuresis and that's driving their water loss.
Speaker: So that's how we approach that patient.
Speaker: If, on the other hand,
Speaker: they have a urine osmality that's very low, let's say it's 100 or 120 or something like that, then they have a water diuresis and diabetes insipidus is in the picture, in the differential diagnosis of that.
Speaker: And then the question is, is it nephrogenic diabetes insipidus or central DI?
Speaker: If it's your brain damaged donor, it's almost certainly central DI.
Speaker: If it's a patient, for example, who has been on lithium for the last 20 years for bipolar disorder,
Speaker: and they went to the OR and they can't take, and they have no access to water now because they're intubated, their nephrogenic DI may now be unmasking itself.
Speaker: Patients with nephrogenic DI are able to keep up with their water losses just by drinking water all day and all night.
Speaker: And they come in with normal sodium.
Speaker: They go to the OR, they get intubated or whatever, and they can no longer drink.
Speaker: And all of a sudden they're putting out the same amount of urine
Speaker: a very hypotonic urine and now they're no longer drinking and they get hypernatremic.
Speaker: So we've seen that, I don't want to say commonly, but we've seen it enough so that it's sort of a syndrome.
Speaker: So that's the way we approach it.
Speaker: Polyuria hypernatremia, what's driving the urine output?
Speaker: Is it a solute diuresis or is it really a water diuresis?
Speaker: If it's a water diuresis, DI is in the picture.
Speaker: If you think it's central diabetes insipidus, then you give them vasopressin and see if they can concentrate their urine.
Speaker: If they can concentrate their urine, then they have central DI.
Speaker: Excellent.
Speaker: And is there anything else that you want to mention regarding the treatment of hypernatremia specifically?
Speaker: Yeah, so the question has always come up, you know, what's the proper rate of correction?
Speaker: Well, there are two things I want to mention.
Speaker: One is estimating what the water deficit is.
Speaker: So we often get, we nephrologists get consulted in the ICU because they say, you know, the patient came in with a sodium of 165 and we've been giving the patient water.
Speaker: But, you know, the patient's sodium concentration is still 162 today.
Speaker: You know, what's the problem?
Speaker: And we say, well, you never did the calculation for their water deficits.
Speaker: And you never, you didn't realize that they had a water deficit of six liters.
Speaker: You know, in other words, people way underestimate what the water deficit is if they don't calculate it.
Speaker: So I strongly encourage people to actually do the calculation for the water deficit.
Speaker: And you can find the formula in lots of different places.
Speaker: It's very easy to do.
Speaker: It's just arithmetic.
Speaker: So do that water deficit calculation.
Speaker: Then the question is, how quickly should you correct them?
Speaker: And the myth that's grown up over the last couple of decades, and it's mostly a mirror effect from this hyponatremia correction thing,
Speaker: is you should definitely not overcorrect them and definitely not correct them more than 8 milliequivalents in the first 24 hours or 0.5 milliequivalents per liter per hour or a whole bunch of things that have crept into the literature around this hyponatremia correction.
Speaker: The truth is there are no data.
Speaker: There are no data.
Speaker: So you can kind of pick your rate.
Speaker: I think a reasonable rate, and I'm on firm grounds here because Rick Stearns from Rochester, who I consider to be the water guru, just wrote a paper on this last month, thinks that 10 milliequivalents in 24 hours is about right.
Speaker: And he's just kind of naming that arbitrarily.
Speaker: But if he wants to go there, then I'm going there.
Speaker: So 10 milliequivalents in 24 hours probably is a safe rate of correction.
Speaker: So it is, in a way, kind of a mirror.
Speaker: It's also a good number, right?
Speaker: Because you only have to remember one number for both cases.
Speaker: Exactly right.
Speaker: That's always helpful.
Speaker: So I guess one of the situations that I just want to touch before we move on is regarding the patients who have severe hypolemia.
Speaker: with hypernatremia, right?
Speaker: Because in that case, as an intensivist, my goal is always to correct the volume status and try to improve perfusion first.
Speaker: And there's been a lot of debate lately, I mean, in the literature about what is the best IV fluid solution for critically ill patients.
Speaker: Based on some very large studies, balanced electrolyte solution seems to have some sort of advantage that can be demonstrated over 15,000 patients.
Speaker: But also a common question you might get from nursing is, why are we giving normal saline?
Speaker: Why are we giving ringers lactate if the patient's hypernatremic?
Speaker: And I think any comments on how you would proceed with somebody who's severely hypovolemic?
Speaker: Yeah, I'm with you.
Speaker: I would correct their volume deficit first, defend their circulation first.
Speaker: And if you give normal saline or lactate ringers, at least you are kind of reassured under most circumstances that
Speaker: that their hypernatremia is not going to get any worse.
Speaker: There is a situation in which the hypernatremia can get worse, and that is in patients who present with hyperosmolar hyperglycemic state.
Speaker: In those people, the hypernatremia is likely to get worse when you volume expand them with an isotonic electrolyte solution.
Speaker: because you're driving the glucose, you're allowing them to get rid of their glucose.
Speaker: Uh, and, uh, and with that goes some water and you're replacing that electrolyte free water with, uh, electrolyte containing water.
Speaker: So they're, they're, their sodium concentration is going to go up under those circumstances.
Speaker: Is that a bad thing?
Speaker: No, it's not bad because their total osmolality is not going to go up.
Speaker: Uh, you've just exchanged some glucose for electrolyte.
Speaker: Um, so, uh,
Speaker: Under most circumstances, in fact, under all circumstances, I would defend the plasma volume or the extracellular fluid volume first.
Speaker: And then when that dust settles, then deal with their osmolality.
Speaker: And at that point, maybe, like you said, with a proper calculation of water deficit plan, how do I get there over the next 24 hours and correct it?
Speaker: That's right.
Speaker: And how do I get there has to do with estimating what their ongoing water losses are.
Speaker: their ongoing water losses.
Speaker: And the ongoing water losses are mostly urinary, but in some people who have big GI losses, you have to account for those.
Speaker: So ongoing water losses, you have to replace completely, 100%, and then you want to replace a certain percentage of their water deficit in order to begin to bring their sodium down.
Speaker: So that's the conceptual approach to these folks.
Speaker: How do you bring them down?
Speaker: replace their ongoing water losses completely, and then a certain proportion of their water deficit.
Speaker: So I think we could go on talking about this for a lot longer, Larry, but I want to be obviously very respectful of your time.
Speaker: And what we'd like to do at Critical Matters is to end the podcast with some questions that are unrelated to the topic, the clinical topic we discussed.
Speaker: Would that be okay?
Speaker: Sure.
Speaker: Yeah, sure.
Speaker: So the first question, Larry, is what book or books have influenced you the most or what book have you gifted most often to others?
Speaker: Well, this is pretty nerdy, but there's a book that was written by a physiologist named Homer Smith, who a lot of people think is the father of modern nephrology.
Speaker: He was a very, he was a brilliant guy whose thoughts really ran very broadly across, from physiology into all kinds of realms.
Speaker: And he wrote a book called From Fish to Philosopher, where he looked at this sort of ontological development of kidneys, but then sort of went on to sort of talk about the philosophical implications of
Speaker: And I've given that book to lots and lots of fellows.
Speaker: It's out of print.
Speaker: And so you have to find it on either eBay or Amazon or something.
Speaker: But that's a, that's a very influential book.
Speaker: And then there's one thinker that really had a huge influence on me in my youth.
Speaker: And I, I still think about him a lot.
Speaker: And that is Buckminster Fuller.
Speaker: Buckminster Fuller is a,
Speaker: was an architect, engineer, inventor, writer, who was born with terrible vision, really terrible vision.
Speaker: And as a result, he kind of always saw the big picture and was able to ask really fundamental questions and look at them from a novel perspective that other people just couldn't do because they were down in the weeds, I think.
Speaker: and came up with some really brilliant ideas about how the world works and how the world could work better.
Speaker: And one of the things he said, which I've carried around with me all my life, is he said, the things we need to do, we can do.
Speaker: If we need to do something, we can do it.
Speaker: And I think that's a good point.
Speaker: place to come from when you're tackling a problem.
Speaker: Yeah.
Speaker: And I think that the opposite of that, or not the opposite, but a different way of looking at that same concept is I think a Kipling quote that says, if you don't get something in life, there's only two reasons.
Speaker: You weren't willing to pay the price or didn't really want it.
Speaker: So for things that really need to be done, we can get there.
Speaker: So that's a great one.
Speaker: And none of these I have ever heard, Larry, and we had multiple conversations.
Speaker: So I'm excited to try to find these.
Speaker: And I'll definitely link them in the show notes for people to explore who are curious.
Speaker: So that's awesome.
Speaker: The second question.
Speaker: Go ahead.
Speaker: Sorry.
Speaker: Yeah, no, that's great.
Speaker: That's great.
Speaker: The second question is,
Speaker: regarding something that you believe to be true that most people don't believe, whether it be in life or in medicine?
Speaker: Well, this is hard because I don't really consider myself to be sort of a philosopher.
Speaker: Yeah, I don't have a good answer for this one, really.
Speaker: I think I'm generally...
Speaker: I'm a pretty strong believer in conventional wisdom.
Speaker: I think conventional wisdom comes out of a lot of common sense on the part of a lot of people.
Speaker: And I find most of it quite useful.
Speaker: So I'm not sure that I can contribute anything to critical matters in that regard.
Speaker: Fair.
Speaker: And the last question is, what would you want every listener and intensivist who's listening to this podcast to know?
Speaker: One thing.
Speaker: Yeah.
Speaker: Yeah, so I think this is important.
Speaker: Protocols, I mean, you know, emergency medicine folks and critical care folks are big on protocols.
Speaker: And the thing to recognize about protocols is that they work great.
Speaker: They work great for about 85% of patients.
Speaker: And it's our job
Speaker: to understand who's in the 15%.
Speaker: It's our job to understand that.
Speaker: And I'll give you an example, and maybe this is a longer answer than you wanted, but I'll give you an example.
Speaker: A patient with end-stage renal disease on hemodialysis came into the emergency department, and they were extremely hyperglycemic.
Speaker: They had a plasma glucose concentration of about 800.
Speaker: A patient with diabetes, known diabetes,
Speaker: And I got called to the emergency department to see the patient.
Speaker: And when I got down there, I saw that the second bag of normal saline was hanging.
Speaker: And I said, why are you giving normal saline to this patient at this rate of 999 mLs per minute?
Speaker: And the resident said, because it's our protocol for patients who come with hyperglycemic state.
Speaker: And it led to a longer conversation, as you can imagine,
Speaker: But it was a protocol that the resident was following without understanding that this patient was in the 15%.
Speaker: And so I just want to really encourage people to understand that the reason that we are physicians or that we are advanced providers is because we are capable, we have the capability to analyze things carefully and to understand
Speaker: who this individual is in front of me, who is this individual in front of me, and what do they need at this moment, and to step out of the protocol.
Speaker: And I think that's a great point, Larry, because I think it goes beyond protocols.
Speaker: It applies to evidence-based medicine.
Speaker: When you look at whatever we have data for in large randomized trials, that really represents probably what we think is best to do for the majority of patients with that disease.
Speaker: But like you said, there's a small percentage of patients who, for whatever reason, fall out of that realm that might be hurt or might not benefit from that same treatment.
Speaker: And it's our job as experts in that field to recognize that.
Speaker: And I think it's important because the goal of protocols is to minimize unwanted variation, but not to tell us what to do for every single case.
Speaker: Exactly right.
Speaker: Larry, this was a great conversation.
Speaker: Thank you so much for your time.
Speaker: I really appreciate talking with you about this topic and hope to have you back on the podcast to talk about other renal-related topics.
Speaker: Well, that'll be fun.
Speaker: Thanks so much.
Speaker: Thanks again for listening to Critical Matters.
Speaker: Make sure to subscribe to this podcast on iTunes or Google Play.
Speaker: You can also listen at www.soundphysicians.com backslash podcast.
