Managing the Critically-Ill Patient with Hyponatremia Bruce Friedman MD: A low level of sodium in the blood is a physiologic abnormality called hyponatremia. When something is wrong with serum sodium levels, there is a problem. Hyponatremia often goes unrecognized in many clinical circumstances. What we are going really abnormal and the hyponatremia can potentially be life-threatening, especially in critically-ill patients. We will talk about definitions, physiology, and treatment, and go into some specific cases regarding critically-ill patients with hyponatremia.

Early Diagnosis and Intervention in Hyponatremia Patient I am going to speak about early diagnosis and intervention in patients with hyponatremia.

Figure 2.1

We should always start out with a definition when we talk about hyponatremia (Figure 1). The most severe hyponatremia is that in which the serum sodium level is less than 120 milliequivalents per liter (mEq/L). Moderate hyponatremia is 120 to 130 mEq/L, and mild hyponatremia (although that can be a definition that is elusive because, indeed, that is still hyponatremia) is 131 to 135 mEq/L. These conditions are either caused by dilution from increased water retention, or depletion from electrolyte issues with excess water loss, which is usually seen in the severe hyponatremic patient.1 The incidence and consequences of hyponatremia are significant (Figure 2). Hyponatremia involves up to 3 to 6 million persons in the US annually. It can affect 15% to 30% of hospitalized patients, with an average of about 25% of intensive care unit (ICU) patients in most studies that have been done. It is also associated with significant morbidity and mortality, as we will discuss later. The occurrence and consequences of hyponatremia do increase with age.6

The cost of hyponatremia can be substantial. As with any disease state, whether it is a primary or secondary disease, the cost can reach into the billions of dollars annually, as noted in Figure 3. There are many references that actually show the significant increase in costs. So, it behooves us to not only understand hyponatremia, but also understand ways in which we can either treat it or be preemptive and prevent it.11

Figure 1.

Figure 3.1,7-11

A list of common diagnoses associated with hospitalized patients with hyponatremia is shown in Figure 4. What I want to point out to you here is that many of these diagnoses, including septicemia, heart failure, acute myocardial infarction, diabetes, major disorders of electrolytes and acid–base status, and diseases of the lung, occur in the ICU setting.12 Figure 4.12

Then, we have the euvolemic patients, who do not have a problem with sodium. They actually have normal total body sodium levels, and their blood volume is normal as well. These are primarily the patients with syndrome with inappropriate antidiuretic hormone (SIADH), or which I like to call “syndrome of inappropriate vasopressin.” A number of disorders, especially oncologic, pulmonary, and central nervous system disorders, are responsible for SIADH, as well as a number of drug-induced complications, which we’ll talk about in a moment. And, some endocrine abnormalities, like hypothyroidism or adrenal insufficiency. Although, hypothyroidism has to be very severe in order to cause euvolemic hyponatremia. Hypervolemic hyponatremia is often associated with congestive heart failure (CHF). There are some other disease states, such as cirrhosis or nephrotic syndrome, but CHF is the largest diagnostic proof. The key difference here is these patients have too much volume, as well as either normal or slightly elevated sodium levels. Sometimes their sodium levels are highly elevated, but the point is that their solute level is not a problem. These patients do not need to have sodium levels reduced and you do not have to give them sodium, but you have to reduce excess volume in the hypervolemic setting and even in the euvolemic setting. The problem is a volume problem, not a sodium problem.13 The common risk factors for hyponatremia are listed in Figure 6; I have discussed some of the disease states already. The therapies are noted on the left side of this figure.

There are several etiologies of hyponatremia. We have on the left side of Figure 5, hypovolemia. Hypovolemic patients not only have low volume, but they have low serum sodium. These patients have both loss of solute and water, and are usually your more severe hyponatremic patients.

In more detail, the mechanism of drug-induced hyponatremia can include the hypothalamus, which is where vasopressin is made (Figure 7). Hypothalamic vasopressin production can be stimulated by the particular drug classes indicated on the left part of the figure, which then leads to water retention. There are other drugs that work directly on the kidneys. The best examples are the nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs actually block prostaglandins, which are endogenous inhibitors of vasopressin elevation. Unfortunately, if prostaglandins are blocked by 2

NSAIDs, vasopressin levels at the renal tubule will go up and cause hyponatremia. Then there are the diuretics in the green on the far right of the figure, which alter sodium and water homeostasis, either at the proximal loop with the thiazide diuretics, or at the loop of Henle with the loop diuretics such as Lasix and Demadex. Both diuretics will cause water and solute loss, which will come up later when we talk about the cases.20 Figure 5.13

Figure 6.14-19

The clinical challenge in terms of recognition is, how does the hyponatremia present from a symptomatic standpoint? You can see that the number of symptoms increases with the severity of hyponatremia shown in Figure 821. As patients get more hyponatremic, they progress from confusion, fatigue, and headache up to coma, seizures, respiratory arrest, and potentially death. Hyponatremia is a significant morbidity- and mortality-associated problem. As many of you know, confusion and delirium is a huge problem in the ICU and this is a big, but potentially correctable problem potentially associated with hyponatremia.22 When we look at morbidity, focusing on a couple of these symptoms, hyponatremia causes particularly significant cognitive and neurologic impairment, which can lead to falls (Figure 9). In the elderly population, falls can lead to traumatic injuries such as hip fractures or other types of fractures, which many of us have seen clinically.25 On the other side, delirium, which is, again, a very large problem in the ICU population, causes increased length of hospital stay and is also associated with increased mortality due to its other complications, noted here such as aspiration.24

Figure 7.20

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Figure 8.21-22

neurologic implication here of moderate and severe hyponatremia.26 Figure 10.26

Figure 9.23-25

There are many risk factors for delirium, which our ICU patients have (Figure 11). If hyponatremia is one of those risk factors, and is potentially is correctable, then it is something that we really have to consider as part of what we need to treat.27 Figure 11.27

Shown in Figure 10 is a summary of an elegant study done by the Belgium group that looked at hyponatremia as a direct cause of gait instability by measuring the way patients walked on a surface covered by electrodes. You can see on the left side of the figure that the patients with hyponatremia had a marked alteration in gait at the low level of hyponatremia at 124 mEq/L, but there were also marked gait abnormalities at the very mid-range level of hyponatremia at about 130 mEq/L. When these were corrected, gait stability reverted to normal. Given the direct relationship between unsteadiness and potential complications, there has to be a

The impact of delirium is gigantic. It is a huge problem; we see it all the time. Levels range from 20% of the US population to 35%, and again there is literature to support even higher numbers than 4

that. Of course, the annual cost of delirium is in the billions of dollars (Figure 12).28 So, again, if there is a risk factor such as hyponatremia whose treatment may impact delirium, it would behoove us to consider tackling that very closely.28

Figure 13.29

Figure 12.28

Figure 14.30

Hyponatremia is also associated with increased ICU admission and mortality. In a large study in which more than 198,000 patients were treated, there was a 5.5% incidence of hyponatremia. Hyponatremia was not only associated not only with higher ICU admissions, but mechanical ventilation, increased length of stay, and hospital death. The cost per hospital increment per patient was over $2,000 (Figure 13).29 Mild hyponatremia can also increase hospital mortality, as was noted by the results of the study by Walkar summarized on in Figure 14. As you can see at the bottom at the figure, there are still statistically significant increases in hospital mortality in the group of patients whose sodium levels are between 130 and 134 mEq/L, and even in the