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Disorders of Sodium and Water Balance in the ICU
16 Plays6 years ago
Hyponatremia and hypernatremia are common in ICU patients and they are associated with increased morbidity and mortality. In this episode of Critical Matters, we discuss the diagnostic approach and treatment of sodium disorders in the ICU.
Our guest is Dr. Lawrence Weisberg, Head of the Division of Nephrology and Deputy Chair of Medicine at Cooper University Health Care. Dr. Weisberg is also Professor of Medicine and Assistant Dean for Curriculum at the Cooper Medical School of Rowan University, in Camden, New Jersey.
Additional Resources:
Disorders of Plasma Sodium - Causes, Consequences, and Correction: https://bit.ly/2TT9SNB
Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients: https://bit.ly/2P2wxrY
Evidence for Managing Hypernatremia: Is It Just Hyponatremia in Reverse?:
https://bit.ly/2HjZn0S
Books Mentioned in this Episode:
From Fish to Philosopher; the Story of our Internal Environment by Homer William Smith: https://amzn.to/30nrraU
Operating Manual for Spaceship Earth by R. Buckminster Fuller: https://amzn.to/2Z6coWt
Critical Path by R. Buckminster Fuller: https://amzn.to/2MA9vH9
Recommended
Transcript
Introduction to Critical Matters Podcast
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now, your host, Dr. Sergio Zanotti.
Sodium and Water Balance Disorders in ICU
00:00:23
Speaker
Disorders of sodium and water balance are common in critically ill patients.
00:00:27
Speaker
Hyponatremia and hypernatremia are associated with increased morbidity and mortality in ICU patients.
00:00:34
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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.
00:00:45
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Today we will discuss this very important topic.
Guest Introduction: Dr. Lawrence Weisberg
00:00:48
Speaker
Our guest is Dr. Lawrence Weisberg.
00:00:50
Speaker
Dr. Weisberg is the head of the Division of Nephrology and Deputy Chair of Medicine at Cooper University Healthcare.
00:00:56
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He is a professor of medicine and assistant dean for curriculum at the Cooper Medical School of Rowan University in Camden, New Jersey.
00:01:03
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Dr. Weisberg is a phenomenal clinician and a medical educator with a long list of publications in the field.
00:01:08
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It's a true pleasure to have him on the podcast to discuss hypo and hypernatremia.
00:01:13
Speaker
Larry, welcome to Critical Matters.
00:01:16
Speaker
Sergio, thank you so much.
00:01:17
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It's a pleasure to be here.
Understanding Hypo and Hypernatremia
00:01:19
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?
00:01:32
Speaker
No, that's exactly right.
00:01:34
Speaker
A lot of people think that the hypo and hypernatremia are disorders of sodium homeostasis, when in fact that's not true.
00:01:43
Speaker
They really are disorders of water homeostasis.
00:01:46
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And it's important to recognize that.
00:01:49
Speaker
because that's sort of a window into the pathogenesis and pathophysiology of these disorders.
00:01:57
Speaker
And as you point out, these really are common disorders, especially in critically ill patients.
Severity of Hyponatremia in ICU Patients
00:02:03
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.
00:02:13
Speaker
And even severe hyponatremia,
00:02:19
Speaker
which we can talk about what the definitions of that might be, occurs in maybe 5% to 10% of patients.
00:02:27
Speaker
And we're talking about severe, meaning life-threatening hyponatremia.
00:02:32
Speaker
So yeah, these are fairly common disorders.
00:02:36
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
00:02:47
Speaker
disorders of water balance and sodium.
00:02:50
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.
00:02:57
Speaker
So I definitely think it's something that we encounter on a daily basis and is worth, I mean, a deeper dive.
00:03:04
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
00:03:16
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set the framework for our discussion?
Impact of Osmolality Changes on the Brain
00:03:19
Speaker
Sure.
00:03:21
Speaker
So the first thing I like to think about, though, is why do these disorders matter?
00:03:27
Speaker
Like, who cares about hyponatremia?
00:03:29
Speaker
Why should we care?
00:03:31
Speaker
And if you don't mind, I'll start there because I think it might sort of motivate the rest of the discussion.
00:03:37
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I'm happy to talk about the underlying physiology and pathophysiology, but the real question is,
00:03:43
Speaker
Why should we even care about these disorders?
00:03:47
Speaker
So let's take hyponatremia, for example.
00:03:50
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?
00:04:04
Speaker
And understand that there's an osmotic equilibrium between the brain and its extracellular milieu, right?
00:04:12
Speaker
So water...
00:04:13
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permeates this semipermeable membrane.
00:04:17
Speaker
And so you achieve osmotic equilibrium between the extracellular fluid and the intracellular fluid of the brain.
00:04:25
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And what happens when you reduce, for whatever reason, you reduce the extracellular osmolality?
00:04:32
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What happens is, as you can imagine, water moves down its concentration gradient across the semipermeable membrane
00:04:42
Speaker
into the cells.
00:04:43
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?
00:04:54
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Everybody can understand that.
00:04:56
Speaker
Cells swell all over the body.
00:04:58
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.
00:05:09
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And so changes in cell volume in the brain
00:05:12
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get transduced into changes in intracranial pressure.
00:05:16
Speaker
And that's the big problem with hyponatremia, for example, increases in intracranial pressure.
00:05:24
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And those increases in intracranial pressure are proportional to the magnitude of the hyponatremia that develops and the rapidity with which it develops.
00:05:36
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And we can talk more about that later.
Lethality of Hyponatremia in Neuro-ICU Patients
00:05:39
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And the converse happens with hypernatremia.
00:05:41
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So water, again, moves down its concentration.
00:05:44
Speaker
So in this situation, water would move from the intracellular space to the extracellular fluid space, and the brain would shrink.
00:05:53
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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.
00:06:09
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blood vessels.
00:06:10
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That's some concern.
00:06:12
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Whether it's actually borne out in reality remains to be debated, but that's a significant concern.
00:06:19
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Okay, so that's why it matters.
00:06:20
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So it matters because of this brain swelling and shrinking that's associated with changes in
Body Regulation of Water and Sodium Balance
00:06:29
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extracellular fluid osmolality.
00:06:31
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And because sodium is the predominant extracellular osmol, changes in sodium concentration are
00:06:38
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reflected in these changes in osmolality that then have these effects on cell volume.
00:06:43
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Okay, so that's the setup, right?
00:06:45
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That's why we care.
00:06:47
Speaker
And hyponatremia, hypo rather than hyper most of the time, hyponatremia is one of really very few potentially lethal electrolyte abnormalities.
00:07:01
Speaker
That's why we worry about it.
00:07:03
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So, yeah.
00:07:05
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And just to
00:07:06
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.
00:07:26
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.
00:07:36
Speaker
Yeah, I think you're right.
00:07:36
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.
00:07:57
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So let's think about
00:08:01
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normal physiology first, uh, as a way of kind of setting up what the pathophysiology might be that might result in these disorders.
00:08:09
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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,
00:08:32
Speaker
what would happen if you drank three of those right now, just drank them down right now?
00:08:38
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Well, we all know exactly where we would be in probably 10 or 20 minutes.
00:08:44
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And the question is, why?
00:08:47
Speaker
Why does that happen?
00:08:48
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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?
00:08:55
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So let's follow the
00:08:58
Speaker
Let's follow the sort of the steps involved in that process.
00:09:02
Speaker
So what happens is this water is absorbed from your GI tract, right?
00:09:07
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You know, when you drink water, it doesn't result in diarrhea.
00:09:10
Speaker
Thank goodness.
00:09:11
Speaker
That water is absorbed from your GI tract and it's absorbed into the extracellular fluid space.
00:09:18
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And so the osmolality of the extracellular fluid space diminishes just slightly, really very slightly.
00:09:26
Speaker
And that is red,
00:09:27
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by osmoreceptors.
00:09:31
Speaker
There are, in fact, osmoreceptors in the hypothalamus.
00:09:34
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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.
00:09:44
Speaker
And when they swell or shrink, they send either an inhibitory or a stimulatory signal to other nuclei in the hypothalamus to then
00:09:55
Speaker
either down-regulate or up-regulate a signal, and that signal is antidiuretic hormone, ADH, right?
00:10:06
Speaker
So under conditions where those osmoreceptors swell, they send a negative or an inhibitory signal to these nuclei.
00:10:14
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They turn off ADH production by the hypothalamus and basically turn off ADH secretion by the posterior pituitary
00:10:25
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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.
00:10:38
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The collecting duct of the kidney is where urine is concentrated, and it's only concentrated in the presence of vasopressin.
00:10:48
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Vasopressin acts to insert water channels
00:10:52
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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.
00:11:11
Speaker
So that in the presence of high concentrations of ADH, you have a lot of water channels present in the apical membrane.
00:11:17
Speaker
You can reabsorb a lot of water from the filtrate down its concentration gradient
00:11:22
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into the medullary interstitium and you put out a maximally concentrated urine that could have an osmolality as high as 1200 milliozins per liter.
00:11:31
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
00:11:47
Speaker
which could have a urine osmolality as low as 50 milliosms per liter.
00:11:52
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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.
Hyponatremia Diagnosis and Causes
00:12:08
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And it's all in response to the ambient osmolality, right?
00:12:14
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So that's,
00:12:15
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So the flip side is, let's say you get dehydrated, and I want to emphasize that term, dehydration.
00:12:24
Speaker
When nephrologists talk about dehydration, they're talking about hyperosmolality, hyperosmolality, not volume depletion, which is different.
00:12:34
Speaker
We look at that differently.
00:12:36
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I'm talking about dehydration.
00:12:38
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That is a relative lack of water relative to the amount of solute that's available in the
00:12:44
Speaker
body or in the extracellular fluid.
00:12:47
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.
00:13:07
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So that's the underlying physiology.
00:13:11
Speaker
So then the question is, how could that possibly
00:13:15
Speaker
be disrupted.
00:13:15
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And the reality is it's not disrupted.
00:13:18
Speaker
And most of us, we hang out with a plasma osmolality that is more or less the same through our entire lives.
00:13:28
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Most of us have a plasma sodium concentration.
00:13:31
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You know, normal plasma sodium concentration is 135 to 145.
00:13:37
Speaker
But most of us hang out with sodium concentrations between 138 and 142.
00:13:42
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for really our whole lives.
00:13:44
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There's very little fluctuation.
00:13:48
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And that's because this system that I just described works phenomenally well.
00:13:54
Speaker
Let me also say that there's another component to the hyperosmonality side of this.
00:14:01
Speaker
So that, for example, if you're out in the desert hiking and you forgot to bring a lot of water, well,
00:14:10
Speaker
you're going to get pretty dehydrated pretty fast, and you're going to be at a maximum ADH state.
00:14:16
Speaker
And so you're going to put out a very concentrated urine.
00:14:18
Speaker
You're not going to lose any water through your kidneys.
00:14:22
Speaker
But in order to return your plasma osmolality to normal, you're going to have to drink.
00:14:29
Speaker
And in fact, when your plasma osmolality gets high enough, it stimulates the thirst centers in the hypothalamus to drink.
00:14:40
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to stimulate you to drink.
00:14:42
Speaker
And you will drink until your plasma osmolality is recovered to normal.
00:14:49
Speaker
So those are the components of the normal osmoregulatory system in the body.
00:14:57
Speaker
So maybe we can jump into hyponatremia first.
00:15:01
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
00:15:08
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.
00:15:21
Speaker
Sure.
00:15:24
Speaker
So as I said, it's quite common in the ICU.
00:15:27
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.
00:15:39
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.
00:15:54
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.
00:16:05
Speaker
Um, so, uh,
00:16:08
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.
00:16:29
Speaker
So generally speaking,
00:16:34
Speaker
In order to get a sodium concentration less than 135, you have to somehow take in more water than you get rid of.
Secondary Causes of Hyponatremia
00:16:45
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?
00:16:57
Speaker
And the answer is yes, it is possible.
00:17:00
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.
00:17:26
Speaker
So that's really a pretty deceit.
00:17:27
Speaker
I mean, that becomes a full-time job, basically.
00:17:32
Speaker
So most people can't do that.
00:17:34
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.
00:17:42
Speaker
And those people can overwhelm their diluting capacity and develop sometimes really profound hyponatremia.
00:17:49
Speaker
We call that problem primary polydipsia.
00:17:56
Speaker
In the past, we used to call it psychogenic polydipsia.
00:18:00
Speaker
or compulsive water drinking.
00:18:02
Speaker
And now we use a less pejorative term, and we just call it primary polydipsia.
00:18:09
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.
00:18:20
Speaker
But it also depends on how much solute, how much fixed solute you have to get rid of through your kidneys every day.
00:18:30
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.
00:18:51
Speaker
That means that you have to have a certain amount of solute in which that
00:18:57
Speaker
to dissolve in that water that you're going to get rid of is urine.
00:19:01
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.
00:19:24
Speaker
or you can't get rid of as much of that water as you might if you took in more solute-generating stuff.
00:19:33
Speaker
So there are folks who take in a lot of water and very little solute that they have to get rid of.
00:19:42
Speaker
And those people, classically, are really enthusiastic beer drinkers.
00:19:48
Speaker
So there are people who drink liters and liters of beer a day,
00:19:51
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.
00:20:03
Speaker
And they retain that water and therefore they develop hyponatremia.
00:20:09
Speaker
So there is this beer drinker podomania, as it's been called, podomania, meaning a mania for drinking.
00:20:20
Speaker
So the
00:20:21
Speaker
That's a unique situation.
00:20:23
Speaker
We see it in other circumstances or that mechanism kick in in other circumstances, but that's the idea behind it.
00:20:30
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.
00:20:46
Speaker
If their uranosmolality is super low, meaning...
00:20:50
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.
00:21:02
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.
00:21:13
Speaker
Most of the time what we see is a concentrated urine.
00:21:17
Speaker
We see somebody who has
00:21:20
Speaker
low plasma osmolality and has a concentrated urine.
00:21:28
Speaker
So you might say, well, that's completely crazy.
00:21:30
Speaker
How could that possibly happen?
00:21:33
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.
00:21:48
Speaker
So you might say, well, that's crazy.
00:21:50
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?
ADH Release and Hyponatremia Diagnosis
00:22:02
Speaker
And the answer is that there is another physiologic stimulus for ADH release besides osmoregulation.
00:22:13
Speaker
And that is...
00:22:17
Speaker
a hemodynamic or baroreceptor mechanism for the stimulation of ADH.
00:22:23
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.
00:22:41
Speaker
So vasopressin is a vasoconstrictor, and it is
00:22:46
Speaker
released under conditions of low blood pressure or low stretch of baroreceptors, which can occur in severe volume depletion as well.
00:22:57
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.
00:23:12
Speaker
and try to see whether they have a volume stimulus or a baroreceptor stimulus for their high ADH.
00:23:21
Speaker
And that's really based on their physical examination.
00:23:23
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
00:23:40
Speaker
the urinary sodium concentration.
00:23:43
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.
00:23:59
Speaker
And that's typically associated with volume depletion or hypotension.
00:24:05
Speaker
So that's an added piece of information that would tell me, yeah, this person is
00:24:11
Speaker
may have a baroreceptor mechanism for their high ADH state.
00:24:18
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
Diagnostic Tests for Hyponatremia
00:24:34
Speaker
circumstance.
00:24:34
Speaker
Does that make sense?
00:24:36
Speaker
Yep.
00:24:38
Speaker
And how do you, so what would you regularly get?
00:24:42
Speaker
I mean, a lot of times, I guess, you've seen these patterns over and over again, and there's also probably combinations.
00:24:47
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?
00:24:53
Speaker
Is there anything else that you would order in the diagnostic approach?
00:24:57
Speaker
Sure.
00:24:57
Speaker
So, yeah, that's a great question.
00:25:00
Speaker
So the first things that I would order, um,
00:25:05
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.
00:25:18
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.
00:25:31
Speaker
And that is where they have a
00:25:33
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.
00:25:47
Speaker
And the example that I'm sure you're thinking of right now is hyperglycemia.
00:25:53
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
00:26:04
Speaker
as a result of the hyperglycemia.
00:26:07
Speaker
That's hypertonic or hyperosmolar hyponatremia.
00:26:12
Speaker
We don't really worry about that because it's not associated with cell swelling.
00:26:16
Speaker
It's associated with cell shrinkage.
00:26:19
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So we don't worry about the hyponatremia per se.
00:26:22
Speaker
In hospitalized patients, sometimes they're given a solute like that specifically to
00:26:30
Speaker
cause brain shrinkage.
00:26:32
Speaker
And the one that I'm thinking about is mannitol.
00:26:35
Speaker
Sometimes they're giving glycerol as well.
00:26:37
Speaker
And those can do the same thing as glucose.
00:26:40
Speaker
And that is cause water movement out of cells, dilute the sodium in the extracellular fluid space and cause hyponatremia with hyperosmolality.
00:26:50
Speaker
Again, we don't care about the hyponatremia, but, but because you don't measure mannitol or glycerol on a chem seven, um,
00:26:59
Speaker
or a basic chemistry panel, it makes sense in that situation, if there's any concern about that, to measure the plasma osmolality.
00:27:09
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.
00:27:21
Speaker
Once you do that, the next step is to look at the urine osmolality.
00:27:26
Speaker
As I said, if the uranosomal is really low, then it's primary polydipsia or something like buropodomania.
00:27:32
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.
00:27:46
Speaker
And the next step along the way is to try to assess their plasma volume, the extracellular fluid volume and hemodynamics,
00:27:55
Speaker
as I just mentioned.
00:27:56
Speaker
And one of the useful things there is the urine sodium concentration.
00:28:02
Speaker
Sometimes the sodium is not so helpful and you would want to urine chloride as well.
00:28:10
Speaker
And the potassium can also be helpful in the urine for reasons that I'll tell you about in a minute.
00:28:16
Speaker
And so you would check the urinal electrolytes, all the urinal electrolytes.
00:28:20
Speaker
So that's really
00:28:21
Speaker
Those are all the sort of fancy chemicals at this point, right?
00:28:24
Speaker
Just a plasma osmolality, urine osmolality, and urinal electrolytes.
00:28:29
Speaker
And you can get those all at once.
00:28:31
Speaker
That would be very helpful.
00:28:34
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.
00:28:48
Speaker
And that just really muddies the picture for us.
00:28:51
Speaker
So the great thing is to see a patient with hyponatremia and just whammo, get all those studies right off the bat.
00:28:59
Speaker
That would be extremely helpful.
00:29:02
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?
00:29:11
Speaker
Plasma?
00:29:12
Speaker
Yeah, plasma osmolality, uranosmolality, and urine electrolytes.
00:29:17
Speaker
Okay.
00:29:17
Speaker
Okay.
00:29:18
Speaker
Like you said, I mean, that's pretty easy.
00:29:20
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.
00:29:33
Speaker
Excellent.
00:29:33
Speaker
Exactly.
00:29:34
Speaker
Yeah, exactly.
00:29:35
Speaker
Yep.
00:29:37
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,
00:29:47
Speaker
So let's say you have a patient who has true hypotonic hyponatremia.
00:29:53
Speaker
They have a high uranosolality, which is what we see in 95% of the patients in that situation.
00:30:01
Speaker
You assess their volume status and you say, no, this patient's not volume depleted.
00:30:05
Speaker
And in fact, when you measure their urinal electrolytes, they have a lot of electrolyte in there.
00:30:09
Speaker
Say their sodium and potassium concentration is quite high.
00:30:13
Speaker
Let's say it adds up to 100 or more.
00:30:18
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.
00:30:32
Speaker
That is a person who would then fall into the category, possibly, of somebody who has SIADH.
00:30:41
Speaker
And that I, that inappropriate, means inappropriate for both
00:30:45
Speaker
the physiologic regulators of ADH, the Osmo regulation and the Barrow regulation.
00:30:50
Speaker
So that's what that I names, inappropriate for both the physiologic regulators of ADH.
00:30:59
Speaker
And then, so then we walk down the path of SIDH.
00:31:03
Speaker
But in order to get to the path of SIDH, you have to jump over two hurdles.
00:31:08
Speaker
And those two hurdles are two endocrine abnormalities that could potentially result
00:31:15
Speaker
in an ADH-independent urinary concentration.
Differentiating SIADH and Cerebral Salt Wasting
00:31:22
Speaker
And those two endocrine disorders are hypothyroidism and adrenal insufficiency.
00:31:31
Speaker
So both of these, we think, can be associated with urinary concentration even in the absence of ADH.
00:31:40
Speaker
The data there are a little murky, but both of those
00:31:44
Speaker
endocrine abnormalities can be associated with hyponatremia, and so it's useful to look for those anyway.
00:31:53
Speaker
And one of the advantages in critically ill patients is that a spot cortisol can rule it out, right?
00:32:00
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.
00:32:10
Speaker
And...
00:32:12
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.
00:32:23
Speaker
And with thyroid, I mean, getting the thyroid hormone test, you can figure that out as well.
00:32:29
Speaker
Right, right.
00:32:35
Speaker
So one of the, yeah, go ahead.
00:32:38
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.
00:32:50
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
00:33:02
Speaker
Some believe it exists and some don't believe it.
00:33:04
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?
00:33:21
Speaker
Oh, that's right.
00:33:21
Speaker
Yeah.
00:33:22
Speaker
Patients with SIDH typically are subtly volume expanded because they are hanging on to water.
00:33:32
Speaker
And so they're a little bit volume expanded.
00:33:36
Speaker
They have copious electrolyte in the urine.
00:33:40
Speaker
People in whom people would entertain the diagnosis of cerebral salt wasting, those folks typically look volume depleted.
00:33:49
Speaker
But the problem is, you know, I said that the urine electrolyte concentration is
00:33:54
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.
00:34:02
Speaker
They tend to have very low urinary sodium and chloride concentration.
00:34:08
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.
Treatment of Severe Hyponatremia
00:34:19
Speaker
And that's thought to be the primary mechanism for their volume depletion is that there's salt wasting.
00:34:25
Speaker
So it can be really confusing.
00:34:27
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.
00:34:49
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.
00:35:01
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.
00:35:15
Speaker
So it's super confusing to try to understand how to discriminate between the cerebral salt wasting and SIDH.
00:35:23
Speaker
Both are characterized by hyponatremia with a lot of electrolyte in the urine and low serum uric acid levels.
00:35:32
Speaker
So it can be really confusing.
00:35:34
Speaker
And the only discriminating feature really is what happens to them when you restrict their sodium intake.
00:35:45
Speaker
If you restrict the sodium intake of somebody with SIDH, well, eventually they'll come into sodium balance.
00:35:52
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.
00:36:04
Speaker
But somebody with cerebral salt wasting will never reduce their urinary sodium concentration, and they will continue to
00:36:15
Speaker
have a naturesis into a state of volume contraction, I mean, obvious volume contraction.
00:36:24
Speaker
So that's the discriminator.
00:36:26
Speaker
The question is, how do you decide when somebody's volume contracted?
00:36:30
Speaker
And I think that's what you were getting at before.
00:36:32
Speaker
It's often not easy.
00:36:34
Speaker
I mean, we don't have great ways of assessing people's volume status.
00:36:41
Speaker
So it can be quite confusing.
00:36:44
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?
00:36:55
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.
00:37:04
Speaker
Would that be fair?
00:37:06
Speaker
That's exactly right.
00:37:07
Speaker
That is exactly right.
00:37:09
Speaker
So we treat severe symptomatic hyponatremia
00:37:14
Speaker
the same way regardless of what we think the cause might be.
00:37:21
Speaker
And that is to give hypertonic saline.
00:37:25
Speaker
That's the treatment for acute, or not necessarily acute, but severe symptomatic hyponatremia.
00:37:33
Speaker
So your question is, what do we mean by that?
00:37:37
Speaker
What's symptomatic?
00:37:39
Speaker
And the answer is the symptoms really can range from
00:37:44
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?
00:38:10
Speaker
So,
00:38:13
Speaker
And the severity of the symptoms tend to correlate fairly well with the severity of the hyponatremia.
00:38:23
Speaker
But people who have longstanding, like really chronic hyponatremia tend to tolerate their hyponatremia way better than people who develop really acute hyponatremia.
00:38:35
Speaker
And we can talk about who those folks are.
00:38:39
Speaker
But when anybody shows up with any symptoms
00:38:43
Speaker
signs or symptoms that might be construed as being due to cerebral edema, we treat those people as if they have severe hyponatremia.
00:38:57
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.
00:39:14
Speaker
Well, that's a great way to put it.
00:39:19
Speaker
It depends on what the cause of the hyponatremia is.
00:39:23
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.
00:39:35
Speaker
They came back from Thailand where they were eating terrific street food and ended up with this terrible traveler's diarrhea.
00:39:42
Speaker
And their idea of compensating for that was just to drink a lot of water.
00:39:47
Speaker
So they got volume depleted because of all the electrolyte loss.
00:39:50
Speaker
And they were replacing all that just with water.
00:39:52
Speaker
They couldn't get rid of the water because they were in a high ADHD state because it got volume depleted.
00:39:57
Speaker
And they come in hyponatremic, right?
00:39:59
Speaker
So what is the treatment for that patient?
00:40:02
Speaker
The treatment for that, so that patient, just to be clear, would have a concentrated urine.
00:40:07
Speaker
They would have a high urinal osmolality, but they would have very low urine electrolyte concentrations.
00:40:13
Speaker
right?
00:40:13
Speaker
Because they're volume depleted.
00:40:15
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.
00:40:27
Speaker
And immediately they'd be able to dump out that water.
00:40:30
Speaker
So the normal saline in that situation would work perfectly well, perfectly well.
00:40:37
Speaker
So in, in,
00:40:39
Speaker
so to be really clear in that situation, the tip off is the, is the low urine electrolyte concentration.
00:40:46
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.
00:40:56
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.
00:41:08
Speaker
Um,
00:41:09
Speaker
Because there, they don't have a baroreceptor mechanism for their ADH.
00:41:13
Speaker
It's inappropriate ADH even to their baroreceptor mechanism.
00:41:17
Speaker
And so just giving them volume in the form of crystalloid is not going to turn off their ADH.
00:41:25
Speaker
And in fact, there are some people with SIDH whose diluting defect is so bad that giving them normal saline
00:41:36
Speaker
may actually worsen their hyponatremia.
00:41:40
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.
00:42:03
Speaker
They will take that normal saline and they will
00:42:06
Speaker
put out hypertonic saline and reabsorb the water from the saline solution that you give them, and it'll drive their sodium lower.
00:42:15
Speaker
So you have to be really careful about whom you give normal saline to in this situation.
00:42:24
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?
00:42:37
Speaker
Yeah.
00:42:37
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.
00:42:55
Speaker
That's it.
00:42:56
Speaker
Because there's a lot of concern about overcorrection.
00:43:00
Speaker
So how do we give enough...
00:43:04
Speaker
3% saline, in order to do that, it's really trial and error.
00:43:08
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.
00:43:19
Speaker
There'll be plenty of time for re-equilibration.
00:43:23
Speaker
So give 100 mLs of 3% saline as a bolus over 10 minutes and
00:43:32
Speaker
and then recheck the plasma sodium.
00:43:33
Speaker
If it's not where you want, then you can give another 100 mLs and recheck.
00:43:38
Speaker
And your target is an increase of 6 mEq per liter.
00:43:43
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.
00:43:54
Speaker
Don't give them any more 3% saline increase.
00:44:00
Speaker
for the next 24 hours, really just leave them where they are.
Risks of Rapid Hyponatremia Correction
00:44:04
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.
00:44:17
Speaker
And, yeah.
00:44:21
Speaker
And I think that, so that's an important point, right?
00:44:25
Speaker
You just want to make a small change up front
00:44:28
Speaker
And that will be enough to prevent the patient from dying from the consequences of cerebral edema, number one.
00:44:34
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?
00:44:49
Speaker
Yeah, so overcorrection, there's been a huge amount of debate over this for the last
00:44:58
Speaker
30 years, really 30 years, what constitutes overcorrection.
00:45:02
Speaker
And by overcorrection, I mean too rapid correction.
00:45:09
Speaker
I don't mean overshoot, but that can happen too.
00:45:11
Speaker
But I just mean correction that's too rapid.
00:45:15
Speaker
And so I'm just going to give you the bottom line after 30 years of debate about this.
00:45:22
Speaker
The bottom line is
00:45:24
Speaker
that the maximum rate of correction for somebody with severe hyponatremia is no more than 10 milliequivalents in the first 24 hours.
00:45:35
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.
00:45:43
Speaker
Nobody should be corrected more rapidly than that.
00:45:46
Speaker
And the question is why?
00:45:51
Speaker
And the answer is because more rapid correction than that is associated with really catastrophic, can be associated with catastrophic neurologic consequences.
00:46:04
Speaker
And they fall into the category or under the diagnosis of the osmotic demyelination syndrome, ODS.
00:46:13
Speaker
We used to call this central pontine myelinolysis,
00:46:18
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.
00:46:23
Speaker
And so we call it the osmotic demyelination syndrome.
00:46:27
Speaker
And so what does this syndrome look like?
00:46:31
Speaker
It presents typically as motor abnormalities, often involving speech, but other motor abnormalities as well.
00:46:41
Speaker
Sometimes cognitive impairment,
00:46:44
Speaker
And it doesn't show up typically, and this is the sort of really bothersome thing about it.
00:46:52
Speaker
It doesn't show up for anywhere between three and 10 days after the correction of the sodium.
00:47:01
Speaker
So just because the patient the next day looks fine doesn't mean you're out of the woods.
00:47:07
Speaker
And there are certain populations who are predisposed to this, and people should recognize this.
00:47:13
Speaker
So you want to be extra careful in the very young, so kids, the very old.
00:47:22
Speaker
Women, for some reason, are at greater risk than men.
00:47:27
Speaker
People who are malnourished, chronically malnourished.
00:47:30
Speaker
People who are hypokalemic, as well as hyponatremic.
00:47:35
Speaker
And people with a history of alcohol ingestion.
00:47:39
Speaker
Those are the folks who are at most risk of this osmotic demyelination syndrome.
00:47:45
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?
00:47:58
Speaker
I would say, yes.
00:48:00
Speaker
Yes, I think that's right.
00:48:01
Speaker
And the reason that that's right is because the biggest risk in the treatment of hyponatremia is overcorrection.
00:48:09
Speaker
We tend to overcorrect.
00:48:10
Speaker
Yeah.
00:48:12
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.
00:48:25
Speaker
And so I think in these high-risk folks, you should target a lower rate of correction.
00:48:30
Speaker
Yeah, I think that would be totally sensible.
00:48:33
Speaker
And let me clarify a question.
00:48:36
Speaker
When you say that, so let's assume that the target, like you said, is for most patients is overcorrected.
00:48:42
Speaker
a delta or a change of 10 mil equivalents in 24 hours.
00:48:47
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.
00:49:02
Speaker
Is the damage done at that point?
00:49:06
Speaker
I'll tell you that we don't really have any data in human beings about this.
00:49:12
Speaker
We don't know.
00:49:14
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?
00:49:25
Speaker
And the answer is nobody really knows.
00:49:28
Speaker
There's some animal data to show that backing it down is beneficial, but we don't have any human data.
00:49:35
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.
00:49:49
Speaker
That's the real concern.
00:49:50
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.
00:50:04
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.
00:50:25
Speaker
What's happened is you've suppressed their, you've suppressed their ADH by volume expanding them.
00:50:31
Speaker
And so now if you give them water,
00:50:34
Speaker
they'll just get rid of the water, right?
00:50:37
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.
00:50:44
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.
00:50:57
Speaker
And I think this is an important point, Larry, because I do believe that fortunately,
00:51:03
Speaker
especially most young clinicians have not seen one of these cases.
00:51:08
Speaker
So I think that sometimes people tend to think, well, this doesn't make any sense.
00:51:13
Speaker
It's like giving Lasix and fluid, right?
00:51:15
Speaker
I mean, at the same time almost.
00:51:18
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.
00:51:26
Speaker
I think that it definitely merits that type of caution, right?
00:51:31
Speaker
Yes, I couldn't have said it better, and I didn't say it better.
00:51:37
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.
00:51:53
Speaker
Number one is, if somebody has severe symptoms, use small boluses of
00:52:01
Speaker
hypertonic saline.
00:52:02
Speaker
So don't put them on a drip.
00:52:04
Speaker
Just give them 100 cc's, mLs over 10 minutes.
00:52:09
Speaker
Recheck the sodium.
00:52:10
Speaker
See where you are.
00:52:12
Speaker
If needed, give them another 100.
00:52:13
Speaker
Now, probably 300 mLs is probably the limit if you want to increase by 6, right?
00:52:19
Speaker
If you're giving your 6 bolus, probably something's wrong.
00:52:24
Speaker
Yeah, that ought to do it.
00:52:25
Speaker
I mean, that ought to do it in most people.
00:52:27
Speaker
It depends on the size of the individual, but yeah, in most folks, that ought to do it.
00:52:32
Speaker
And so the first point is boluses, small boluses of hypertonic saline.
00:52:37
Speaker
The second point is frequent sodium checks.
00:52:42
Speaker
So not only you know where you are, but you can anticipate what's going on.
00:52:46
Speaker
And what would you recommend in terms of the frequency?
00:52:50
Speaker
Well, it has to be individualized.
00:52:52
Speaker
But I would say in these folks, the changes can happen fairly quickly, especially in people who have, and I want to
00:53:00
Speaker
I want to highlight these people as a special group, the people with the baroreceptor mechanism.
00:53:05
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.
00:53:12
Speaker
And so really those folks, you need to be checking them every probably four hours.
00:53:20
Speaker
That would be a reasonable thing to do.
00:53:24
Speaker
And the last thing I was going to say is, which I think is important,
00:53:27
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.
00:53:39
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.
00:53:52
Speaker
Yes, yes.
00:53:54
Speaker
Now I will, I want to just put a,
00:53:57
Speaker
a plug-in for a special group of patients.
00:54:00
Speaker
And the special group of patients is folks who develop acute, acute severe hyponatremia.
00:54:07
Speaker
And there are two special groups I want to talk about.
00:54:10
Speaker
One is postoperative patients, and especially postoperative young women.
00:54:17
Speaker
For some reason, these folks are at particular risk for developing severe acute hyponatremia postoperatively.
00:54:27
Speaker
if they're given hypotonic fluids in that period.
00:54:30
Speaker
So they can drop their sodium from normal to 115 in a couple of hours.
00:54:37
Speaker
Those people are at extremely high risk of catastrophic cerebral edema.
00:54:45
Speaker
Those people, you want to get them back to 140 as quickly as they got from 140 to 115.
00:54:50
Speaker
You can take them right back up immediately.
00:54:56
Speaker
without any deleterious consequence.
00:54:59
Speaker
And in fact, if you delay the treatment of them, they really can get into serious trouble.
00:55:04
Speaker
And just to point out to our colleagues, these are usually healthy women who might be getting laparoscopic type surgeries.
00:55:12
Speaker
So they're not necessarily critically ill women, right?
00:55:14
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?
00:55:24
Speaker
That is exactly right.
00:55:25
Speaker
These are young, otherwise completely healthy women.
00:55:29
Speaker
And for some reason, they're predisposed to hang on to this water that they get around the time of the surgery.
00:55:36
Speaker
And there are too many cases in the literature of catastrophic outcomes in this population because there was delayed recognition and delayed treatment.
00:55:46
Speaker
And the treatment is get their sodium back up as quickly as possible with hypertonic saline.
00:55:51
Speaker
Okay.
00:55:53
Speaker
And the other group, interestingly enough, is also a healthy population, and that is marathoners.
00:56:02
Speaker
Marathoners who drink, you know, who basically stop at every water station.
00:56:07
Speaker
Those folks can have serious symptomatic hyponatremia at the end of the race.
00:56:14
Speaker
And those people also, because they develop their hyponatremia so quickly, need to be brought up just as quickly as they came down.
00:56:22
Speaker
none of this six in six hours and stop.
00:56:25
Speaker
You get them back to normal.
00:56:28
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.
00:56:39
Speaker
Get those people back up really quickly.
00:56:42
Speaker
Excellent.
00:56:44
Speaker
So I think that...
00:56:46
Speaker
Any other comments you want to make specifically about treating other specific causes of hyponatremia?
00:56:51
Speaker
So we said that acutely we know what the goal is, is to get them out of the danger zone, prevent overcorrection.
00:56:59
Speaker
Any particular specifics for patients, let's say, after 24 hours or 48 hours?
00:57:05
Speaker
Larry?
00:57:09
Speaker
Well, you know, after that period of time, it really depends on what the cause of their hyponatremia was.
00:57:16
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.
00:57:32
Speaker
And there are a couple of interesting adjunctive therapies, but I'm not sure they really
00:57:37
Speaker
would be terribly fascinating to a critical care audience.
00:57:41
Speaker
Unless you think... Well, I think that they're more long-term, so I'll put some references in the show notes.
00:57:48
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.
00:57:57
Speaker
That's right.
00:57:58
Speaker
That's right.
00:57:59
Speaker
V2 receptor antagonist and also these days oral urea,
00:58:04
Speaker
oral urea to increase the non-electrolyte solute in the urine and increase their urinary electrolyte-free water excretion.
00:58:11
Speaker
But that's a non-ICU kind of therapy.
Understanding Hypernatremia
00:58:16
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.
00:58:25
Speaker
It seems that the podcast is going to be the same.
00:58:28
Speaker
But why don't we pivot to hypernatremia
00:58:32
Speaker
and start by defining it.
00:58:33
Speaker
What are the clinical manifestations and maybe how you would approach it in the ICU?
00:58:37
Speaker
Sure.
00:58:38
Speaker
So the hypernatremia is easily defined.
00:58:42
Speaker
I mean, it's a sodium greater than 145.
00:58:43
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
00:59:01
Speaker
the thirst mechanism that I talked about earlier.
00:59:04
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.
00:59:19
Speaker
So it's obvious to wonder then, how can anybody get hypernatremic?
00:59:28
Speaker
And the answer is,
00:59:30
Speaker
it almost always occurs in people who either don't have access to water or don't have an intact thirst mechanism.
00:59:38
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.
00:59:57
Speaker
And some people have called hypernatremia
00:59:59
Speaker
any atrogenic disturbance because it's something that we ought to be able to recognize quickly and be able to intervene on quickly.
01:00:10
Speaker
And the intervention really is almost always just giving enough electrolyte-free water to replace the electrolyte losses that the patient has.
01:00:22
Speaker
So, sorry, the water losses that the patient has.
01:00:28
Speaker
So when we think about patients with hypernatremia, we think about how they might have gotten there.
01:00:36
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?
01:00:46
Speaker
And there are really three ways that they can get there.
01:00:50
Speaker
One is common, and the other two are uncommon.
01:00:53
Speaker
The common way is to lose salt and water
01:00:57
Speaker
but water in excess of salt.
Causes and Diagnosis of Hypernatremia
01:01:01
Speaker
And that usually happens because of GI losses or urinary losses.
01:01:06
Speaker
So for example, if a patient's on a diuretic medication, they lose water in excess of salt.
01:01:12
Speaker
And so if there's no intervention made, they will get progressively hypernatremic.
01:01:20
Speaker
If they lose GI fluids, either diarrhea or upper GI fluids, and those losses are not replaced,
01:01:27
Speaker
they will lose water in excess of electrolyte and get progressively hypernatremic.
01:01:37
Speaker
Those people look volume depleted.
01:01:39
Speaker
They look volume depleted because of the electrolyte loss.
01:01:43
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.
01:01:57
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.
01:02:10
Speaker
So that's the sort of basic approach to the patient with volume depletion associated with hypernatremia.
01:02:22
Speaker
There are some folks, fairly uncommonly, who lose weight
01:02:28
Speaker
essentially pure water.
01:02:32
Speaker
And the sort of paradigm of that is diabetes insipidus, either central DI or nephrogenic DI.
01:02:40
Speaker
Those people lose essentially pure water.
01:02:43
Speaker
And so they tend to look euvolemic.
01:02:47
Speaker
And the reason they look euvolemic is because they have lost electrolyte.
01:02:51
Speaker
And water, if they're just losing pure water, water can be lost from
01:02:56
Speaker
is lost from all body water compartments, including the intracellular space.
01:03:00
Speaker
And so they can get pretty hypernatremic and have very little extracellular or intravascular volume loss.
01:03:11
Speaker
Does that make sense?
01:03:13
Speaker
Yep.
01:03:13
Speaker
And I think that DI is not something that we see very commonly in general ICUs.
01:03:21
Speaker
I think, again, it's something that we see much more in people who have
01:03:24
Speaker
significant brain damage or certain types of neurosurgeries, they're very sensitive about the eye because they can expect it almost.
01:03:32
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.
01:03:51
Speaker
These are patients who obviously on one hand
01:03:55
Speaker
are dead, but we are trying to preserve the organs for donation, and these patients commonly will develop DI.
01:04:02
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.
01:04:12
Speaker
Could you talk a little bit more about how you would treat or recognize these patients?
01:04:16
Speaker
Sure.
01:04:17
Speaker
So the way that diabetes insipidus typically shows up is with polyuria,
01:04:22
Speaker
So polyuria associated with hypernatremia.
01:04:27
Speaker
And the worry is, and we get called not uncommonly for that exact situation, the worry is diabetes insipidus.
01:04:40
Speaker
So the question is, is there a differential diagnosis for polyuria and hypernatremia?
01:04:45
Speaker
And the answer is, yes, there is a differential diagnosis.
01:04:49
Speaker
And the differential diagnosis includes
01:04:52
Speaker
polyuria because of a non-electrolyte osmotic diuresis versus a water diuresis like diabetes insipidus.
01:05:04
Speaker
So what do I mean by a non-electrolyte osmotic diuresis?
01:05:08
Speaker
What I mean is, and the obvious one here is, somebody who's extremely hyperglycemic.
01:05:14
Speaker
Hyperglycemia.
01:05:16
Speaker
Hyperglycemia will drive an osmotic diuresis.
01:05:19
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.
01:05:30
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,
01:05:49
Speaker
And they have to get rid of that urea through the kidney.
01:05:51
Speaker
So that generates a non-electrolyte osmotic diuresis.
01:05:56
Speaker
And they become hypernatremic.
01:05:58
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.
01:06:09
Speaker
Is it mostly water or is it mostly solute?
01:06:12
Speaker
And so we check the osmolality of that urine that's coming out, that copious urine.
01:06:20
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.
01:06:30
Speaker
And then the question is, what's the osmo?
01:06:32
Speaker
Is it electrolyte or non-electrolyte?
01:06:34
Speaker
And so we send the urine for electrolytes.
01:06:37
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.
01:06:45
Speaker
This is somebody who
01:06:46
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.
01:06:58
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.
01:07:12
Speaker
So that's how we approach that patient.
01:07:14
Speaker
If, on the other hand,
01:07:15
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.
01:07:30
Speaker
And then the question is, is it nephrogenic diabetes insipidus or central DI?
01:07:34
Speaker
If it's your brain damaged donor, it's almost certainly central DI.
01:07:39
Speaker
If it's a patient, for example, who has been on lithium for the last 20 years for bipolar disorder,
01:07:45
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.
01:07:57
Speaker
Patients with nephrogenic DI are able to keep up with their water losses just by drinking water all day and all night.
01:08:04
Speaker
And they come in with normal sodium.
01:08:07
Speaker
They go to the OR, they get intubated or whatever, and they can no longer drink.
01:08:11
Speaker
And all of a sudden they're putting out the same amount of urine
01:08:15
Speaker
a very hypotonic urine and now they're no longer drinking and they get hypernatremic.
Correcting Hypernatremia
01:08:22
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.
01:08:30
Speaker
So that's the way we approach it.
01:08:32
Speaker
Polyuria hypernatremia, what's driving the urine output?
01:08:37
Speaker
Is it a solute diuresis or is it really a water diuresis?
01:08:40
Speaker
If it's a water diuresis, DI is in the picture.
01:08:44
Speaker
If you think it's central diabetes insipidus, then you give them vasopressin and see if they can concentrate their urine.
01:08:52
Speaker
If they can concentrate their urine, then they have central DI.
01:08:57
Speaker
Excellent.
01:08:58
Speaker
And is there anything else that you want to mention regarding the treatment of hypernatremia specifically?
01:09:07
Speaker
Yeah, so the question has always come up, you know, what's the proper rate of correction?
01:09:12
Speaker
Well, there are two things I want to mention.
01:09:14
Speaker
One is estimating what the water deficit is.
01:09:20
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.
01:09:33
Speaker
But, you know, the patient's sodium concentration is still 162 today.
01:09:38
Speaker
You know, what's the problem?
01:09:41
Speaker
And we say, well, you never did the calculation for their water deficits.
01:09:45
Speaker
And you never, you didn't realize that they had a water deficit of six liters.
01:09:50
Speaker
You know, in other words, people way underestimate what the water deficit is if they don't calculate it.
01:09:58
Speaker
So I strongly encourage people to actually do the calculation for the water deficit.
01:10:03
Speaker
And you can find the formula in lots of different places.
01:10:07
Speaker
It's very easy to do.
01:10:09
Speaker
It's just arithmetic.
01:10:12
Speaker
So do that water deficit calculation.
01:10:15
Speaker
Then the question is, how quickly should you correct them?
01:10:20
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,
01:10:34
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.
01:10:59
Speaker
The truth is there are no data.
01:11:01
Speaker
There are no data.
01:11:05
Speaker
So you can kind of pick your rate.
01:11:07
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.
01:11:26
Speaker
And he's just kind of naming that arbitrarily.
01:11:34
Speaker
But if he wants to go there, then I'm going there.
01:11:37
Speaker
So 10 milliequivalents in 24 hours probably is a safe rate of correction.
01:11:42
Speaker
So it is, in a way, kind of a mirror.
01:11:45
Speaker
It's also a good number, right?
01:11:46
Speaker
Because you only have to remember one number for both cases.
01:11:50
Speaker
Exactly right.
01:11:52
Speaker
That's always helpful.
01:11:55
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.
01:12:04
Speaker
with hypernatremia, right?
01:12:05
Speaker
Because in that case, as an intensivist, my goal is always to correct the volume status and try to improve perfusion first.
01:12:14
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.
01:12:24
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.
01:12:33
Speaker
But also a common question you might get from nursing is, why are we giving normal saline?
01:12:38
Speaker
Why are we giving ringers lactate if the patient's hypernatremic?
01:12:41
Speaker
And I think any comments on how you would proceed with somebody who's severely hypovolemic?
01:12:47
Speaker
Yeah, I'm with you.
01:12:48
Speaker
I would correct their volume deficit first, defend their circulation first.
01:12:53
Speaker
And if you give normal saline or lactate ringers, at least you are kind of reassured under most circumstances that
01:13:01
Speaker
that their hypernatremia is not going to get any worse.
01:13:04
Speaker
There is a situation in which the hypernatremia can get worse, and that is in patients who present with hyperosmolar hyperglycemic state.
01:13:14
Speaker
In those people, the hypernatremia is likely to get worse when you volume expand them with an isotonic electrolyte solution.
01:13:27
Speaker
because you're driving the glucose, you're allowing them to get rid of their glucose.
01:13:32
Speaker
Uh, and, uh, and with that goes some water and you're replacing that electrolyte free water with, uh, electrolyte containing water.
01:13:40
Speaker
So they're, they're, their sodium concentration is going to go up under those circumstances.
01:13:44
Speaker
Is that a bad thing?
01:13:45
Speaker
No, it's not bad because their total osmolality is not going to go up.
01:13:50
Speaker
Uh, you've just exchanged some glucose for electrolyte.
01:13:53
Speaker
Um, so, uh,
01:13:55
Speaker
Under most circumstances, in fact, under all circumstances, I would defend the plasma volume or the extracellular fluid volume first.
01:14:03
Speaker
And then when that dust settles, then deal with their osmolality.
01:14:07
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?
01:14:17
Speaker
That's right.
01:14:18
Speaker
And how do I get there has to do with estimating what their ongoing water losses are.
01:14:24
Speaker
their ongoing water losses.
01:14:25
Speaker
And the ongoing water losses are mostly urinary, but in some people who have big GI losses, you have to account for those.
01:14:33
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
Personalized Care in Intensive Settings
01:14:48
Speaker
down.
01:14:48
Speaker
So that's the conceptual approach to these folks.
01:14:50
Speaker
How do you bring them down?
01:14:52
Speaker
replace their ongoing water losses completely, and then a certain proportion of their water deficit.
01:15:02
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.
01:15:09
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.
01:15:18
Speaker
Would that be okay?
01:15:20
Speaker
Sure.
01:15:20
Speaker
Yeah, sure.
01:15:21
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?
01:15:35
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.
01:15:53
Speaker
He was a very, he was a brilliant guy whose thoughts really ran very broadly across, from physiology into all kinds of realms.
01:16:06
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
01:16:22
Speaker
And I've given that book to lots and lots of fellows.
01:16:25
Speaker
It's out of print.
01:16:26
Speaker
And so you have to find it on either eBay or Amazon or something.
01:16:32
Speaker
But that's a, that's a very influential book.
01:16:36
Speaker
And then there's one thinker that really had a huge influence on me in my youth.
01:16:43
Speaker
And I, I still think about him a lot.
01:16:45
Speaker
And that is Buckminster Fuller.
01:16:48
Speaker
Buckminster Fuller is a,
01:16:50
Speaker
was an architect, engineer, inventor, writer, who was born with terrible vision, really terrible vision.
01:17:00
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.
01:17:20
Speaker
and came up with some really brilliant ideas about how the world works and how the world could work better.
01:17:28
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.
01:17:41
Speaker
If we need to do something, we can do it.
01:17:44
Speaker
And I think that's a good point.
01:17:48
Speaker
place to come from when you're tackling a problem.
01:17:51
Speaker
Yeah.
01:17:52
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.
01:18:04
Speaker
You weren't willing to pay the price or didn't really want it.
01:18:07
Speaker
So for things that really need to be done, we can get there.
01:18:10
Speaker
So that's a great one.
01:18:12
Speaker
And none of these I have ever heard, Larry, and we had multiple conversations.
01:18:15
Speaker
So I'm excited to try to find these.
01:18:18
Speaker
And I'll definitely link them in the show notes for people to explore who are curious.
01:18:22
Speaker
So that's awesome.
01:18:24
Speaker
The second question.
01:18:26
Speaker
Go ahead.
01:18:26
Speaker
Sorry.
01:18:27
Speaker
Yeah, no, that's great.
01:18:28
Speaker
That's great.
01:18:29
Speaker
The second question is,
01:18:31
Speaker
regarding something that you believe to be true that most people don't believe, whether it be in life or in medicine?
01:18:40
Speaker
Well, this is hard because I don't really consider myself to be sort of a philosopher.
01:18:45
Speaker
Yeah, I don't have a good answer for this one, really.
01:18:56
Speaker
I think I'm generally...
01:19:00
Speaker
I'm a pretty strong believer in conventional wisdom.
01:19:03
Speaker
I think conventional wisdom comes out of a lot of common sense on the part of a lot of people.
01:19:08
Speaker
And I find most of it quite useful.
01:19:12
Speaker
So I'm not sure that I can contribute anything to critical matters in that regard.
01:19:19
Speaker
Fair.
01:19:19
Speaker
And the last question is, what would you want every listener and intensivist who's listening to this podcast to know?
01:19:28
Speaker
One thing.
01:19:28
Speaker
Yeah.
01:19:33
Speaker
Yeah, so I think this is important.
01:19:39
Speaker
Protocols, I mean, you know, emergency medicine folks and critical care folks are big on protocols.
01:19:47
Speaker
And the thing to recognize about protocols is that they work great.
01:19:52
Speaker
They work great for about 85% of patients.
01:19:57
Speaker
And it's our job
01:19:58
Speaker
to understand who's in the 15%.
01:20:02
Speaker
It's our job to understand that.
01:20:05
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.
01:20:11
Speaker
A patient with end-stage renal disease on hemodialysis came into the emergency department, and they were extremely hyperglycemic.
01:20:21
Speaker
They had a plasma glucose concentration of about 800.
01:20:24
Speaker
A patient with diabetes, known diabetes,
01:20:29
Speaker
And I got called to the emergency department to see the patient.
01:20:32
Speaker
And when I got down there, I saw that the second bag of normal saline was hanging.
01:20:38
Speaker
And I said, why are you giving normal saline to this patient at this rate of 999 mLs per minute?
01:20:46
Speaker
And the resident said, because it's our protocol for patients who come with hyperglycemic state.
01:20:53
Speaker
And it led to a longer conversation, as you can imagine,
01:20:57
Speaker
But it was a protocol that the resident was following without understanding that this patient was in the 15%.
01:21:06
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
01:21:26
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.
01:21:36
Speaker
And I think that's a great point, Larry, because I think it goes beyond protocols.
01:21:41
Speaker
It applies to evidence-based medicine.
01:21:43
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.
01:21:54
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.
01:22:05
Speaker
And it's our job as experts in that field to recognize that.
01:22:09
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.
Podcast Conclusion
01:22:19
Speaker
Exactly right.
01:22:22
Speaker
Larry, this was a great conversation.
01:22:24
Speaker
Thank you so much for your time.
01:22:26
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.
01:22:33
Speaker
Well, that'll be fun.
01:22:34
Speaker
Thanks so much.
01:22:37
Speaker
Thanks again for listening to Critical Matters.
01:22:39
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.
01:22:43
Speaker
You can also listen at www.soundphysicians.com backslash podcast.