Manifestations of hyponatremia and hypernatremia in adults

INTRODUCTION — Symptoms of hyponatremia or hypernatremia are primarily neurologic. They are related to the severity and, in particular, the rapidity of the change in the serum sodium concentration [1-3]. Patients with hyponatremia and hypernatremia may also have complaints related to concurrent volume depletion and possible underlying neurologic diseases that predispose to the electrolyte abnormality. These include a wide variety of neurologic disorders that can lead sequentially to either the inappropriate secretion of antidiuretic hormone, water retention, and hyponatremia, or to the lack of expression of thirst, which is normally the major protective mechanism against the development of hypernatremia.

The cerebral adaptation and clinical manifestations of hyponatremia and hypernatremia will be reviewed here. The etiology and treatment of hyponatremia and hypernatremia are presented elsewhere:

●(See "Causes of hypotonic hyponatremia in adults".)

●(See "Overview of the treatment of hyponatremia in adults".)

●(See "Etiology and evaluation of hypernatremia in adults".)

●(See "Treatment of hypernatremia in adults".)

HYPONATREMIA — The symptoms directly attributable to hyponatremia primarily occur with acute and marked reductions in the serum sodium concentration and reflect neurologic dysfunction induced by cerebral edema [1,2,4,5], and possibly adaptive responses of brain cells to osmotic swelling [1]. In this setting, the associated fall in serum osmolality creates an osmolal gradient that favors water movement into the cells, leading to brain edema.

The development of cerebral edema in hyponatremic patients is dependent upon the transfer of water from plasma and cerebrospinal fluid into the brain. Insight into this process is provided by studies in mice without the genes for aquaporin-4, a water channel expressed at the interface between the brain and blood and between the brain and cerebrospinal fluid [6]. Compared with wild-type mice, knockout mice exhibit considerably less brain edema, morbidity, and mortality after the induction of acute hyponatremia, suggesting that aquaporin-4 mediates a substantial portion of osmotic water transport into the brain.

Hyponatremia-induced cerebral edema occurs primarily with rapid reductions in the serum sodium concentration, usually less than 24 hours [5], as most often occurs in postoperative patients given large quantities of hypotonic fluid and in patients with self-induced water intoxication due to primary polydipsia or exercise-associated hyponatremia. Hypoxic brain injury also may contribute to the neurologic deficit if respiratory arrest has occurred [7]. (See "Exercise-associated hyponatremia".)

Importance of hypoosmolality in symptom development — Hyponatremia is almost always associated with hypoosmolality, and it is the fall in plasma osmolality that promotes the movement of water into the cells and the possible development of cerebral edema. The contribution of hyponatremia itself to the neurologic manifestations is uncertain. This is an important issue, since there are a variety of settings in which hyponatremia is associated with a normal or high measured serum osmolality. These disorders are discussed in detail separately. (See "Causes of hypotonic hyponatremia in adults".)

Summarized briefly:

●In pseudohyponatremia, both the serum osmolality and the concentration of sodium in plasma water are normal, and patients are asymptomatic. Such patients have either hyperproteinemia or hyperlipidemia, which reduce the fraction of the plasma that is water from the normal value of 93 percent (the remaining 7 percent is due to proteins and lipids with a small contribution from dissolved solutes) to a lower value that can be less than 80 percent. In such settings, the physiologically important sodium concentration per liter of plasma water is normal, although the sodium concentration per liter of plasma is reduced. The plasma osmolality is normal because osmometers measure the activity of solutes in plasma water.

●With moderate to advanced kidney function impairment or with ethanol intoxication, hyponatremic patients may have a higher osmolality than that predicted by their sodium concentration due to the contribution of urea or ethanol in the extracellular fluid. However, urea and ethanol are ineffective osmoles since they can freely cross cell membranes and therefore do not obligate water movement out of the cells. Thus, the effective serum osmolality (measured osmolality minus the contribution of urea or ethanol) in such patients is low. As a result, hyponatremic patients with kidney failure or ethanol intoxication are as likely to develop symptoms at a given serum sodium concentration as patients without these conditions. (See "Causes of hypotonic hyponatremia in adults".)

●In patients with uncontrolled diabetes, the serum osmolality is typically elevated. In contrast to urea, glucose is an effective osmole since it does not freely enter cells. The increase in effective serum osmolality pulls water out of the cells and lowers the serum sodium by dilution, an effect that may be at least partially reversed by the free water loss resulting from the associated glucosuria-induced osmotic diuresis. The neurologic symptoms in these patients are not generated by the hyponatremia since the effective plasma osmolality is usually increased rather than reduced. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Serum sodium' and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Neurologic symptoms'.)

●Isosmotic (or near isosmotic) non-sodium containing, nonconductive irrigation solutions containing glycine, mannitol, or sorbitol may be used during transurethral resection of the prostate or bladder, during hysteroscopy, or laparoscopic surgery. Only a small quantity of this solution is usually absorbed systemically. However, large amounts of the irrigant are occasionally infused by accident into veins or body cavities. Severe hyponatremia due to dilution can result (serum sodium less than 110 mEq/L). Severe neurologic symptoms can occur, but the cause varies, depending upon the irrigant used. Absorption of sorbitol irrigants eventually results in hypotonic hyponatremia as the sorbitol is metabolized. Most glycine irrigants are hypo-osmolar, and absorption of large volumes of the irrigant results in a modest degree of hypotonic hyponatremia; however, in addition to hyponatremia, glycine toxicity and the accumulation of ammonia, serine, and/or glyoxylate from the metabolism of glycine may contribute to neurologic manifestations. (See "Hyponatremia following transurethral resection, hysteroscopy, or other procedures involving electrolyte-free irrigation", section on 'Pathogenesis of neurologic symptoms'.)

Clinical manifestations of acute hyponatremia — The severity of symptoms in patients with acute hyponatremia generally reflects the severity of cerebral overhydration, which is related to the degree of hyponatremia [2]. The major clinical manifestations of acute hyponatremia include [1,2,7-11]:

●Nausea and malaise, which are the earliest findings, may be seen when the serum sodium concentration falls below 125 to 130 mEq/L.

●Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest can occur if the serum sodium concentration falls below 115 to 120 mEq/L. Noncardiogenic pulmonary edema has also been described.

Acute hyponatremic encephalopathy may be reversible, but permanent neurologic damage or death can occur, particularly in premenopausal females [7,10]. Overly rapid correction also may be deleterious, particularly in patients with chronic hyponatremia. (See 'Susceptibility of premenopausal females' below and 'Osmotic demyelination' below.)

Osmolytes and cerebral adaptation to hyponatremia — The degree of cerebral edema and therefore the severity of neurologic symptoms are much less with chronic hyponatremia [2,12,13]. This protective response, which begins on the first day and is complete within several days, occurs in two major steps.

●The initial cerebral edema raises the interstitial hydraulic pressure, creating a gradient for extracellular fluid movement out of the brain into the cerebrospinal fluid [14].

●The brain cells then lose solutes, leading to the osmotic movement of water out of the cells and a decrease in brain swelling [4,5,12,14-18]. Brain cell potassium is lost rapidly through normally quiescent cation channels in the cell membrane that are activated by cell swelling. Subsequently, organic solutes (called organic osmolytes) are lost via swelling-activated membrane channels that also transport chloride and other anions [4,15]. Substantial depletion of brain organic osmolytes occurs within 24 hours, and additional losses occur over two to three days owing to downregulation of the synthesis and uptake of these solutes [4,5].

These processes are reversed with correction of the hyponatremia [4,5,18]. However, the reuptake of brain solutes during correction occurs more slowly than the loss of brain solutes during the onset of hyponatremia.

Organic osmolytes account for approximately one-third of the solute loss in chronic hyponatremia (figure 1) [17]. Reducing the intracellular content of these solutes has the advantage of restoring cell volume without interfering with protein function. By comparison, there would be a potentially deleterious effect on protein function if the volume adaptation were mediated entirely by changes in the cell cation (potassium plus sodium) concentration.

Studies in hyponatremic animals have shown that the major osmolytes lost from the brain cells are the amino acids glutamine, glutamate, and taurine, and, to a lesser degree, the carbohydrate myoinositol [5,16,17]. A study using proton NMR spectroscopy found a slightly different pattern in humans with chronic hyponatremia; myoinositol and choline compounds were the primary organic solutes lost, with a smaller change occurring in glutamine and glutamate [18]. Myoinositol also appears to be the primary osmolyte taken up by the brain as part of the protective response in patients with hypernatremia. (See 'Cerebral adaptation to hypernatremia' below.)

Clinical manifestations of chronic hyponatremia — The cerebral adaptation permits patients with chronic hyponatremia to appear to be asymptomatic despite a serum sodium concentration below 120 mmol/L. When symptoms do occur in patients with serum sodium concentrations at this level, they are relatively nonspecific [1,9,19-22]:

●Fatigue

●Nausea

●Dizziness

●Vomiting

●Gait disturbances

●Forgetfulness

●Confusion

●Lethargy

●Muscle cramps

Nausea and vomiting affect approximately one-third of patients with chronic hyponatremia who have a serum sodium concentration <120 mmol/L [20-22]. Nausea and vomiting can be ominous symptoms of life-threatening cerebral edema in patients with acute hyponatremia; by contrast, in chronic hyponatremia, these symptoms are not associated with adverse outcomes. Seizures and coma are uncommon and often reflect an acute exacerbation of the hyponatremia. Symptomatic chronic hyponatremia is rarely, if ever, associated with cerebral edema severe enough to cause herniation of the brain. In a series of 223 patients hospitalized for symptomatic chronic hyponatremia due to thiazide diuretics, there was a 1 percent incidence of seizures and no cases of herniation [20]. (See "Diuretic-induced hyponatremia".)

The older literature includes reports of brain damage in outpatients with thiazide-induced hyponatremia [8]. However, at the time of the study, the consequences of overly rapid correction were unknown. The reported patients were all treated with hypertonic saline, increasing the serum sodium concentration by more than 25 mEq/L in 48 hours, a rate of correction that is associated with osmotic demyelination. (See 'Osmotic demyelination' below.)

Subtle manifestations in mild to moderate chronic hyponatremia — Patients with moderate chronic hyponatremia often appear asymptomatic but may have subtle neurologic manifestations that can easily be missed. These manifestations may be consequences of the brain's adaptations to hyponatremia that make survival possible [23]. The following observations illustrate the range of findings:

●The SALT-1 and SALT-2 trials evaluated the efficacy of the oral vasopressin receptor antagonist tolvaptan compared with placebo in patients with chronic hyponatremia; none of the patients had clinically apparent neurologic symptoms at baseline and almost all had a serum sodium concentration of 120 mEq/L or higher [24]. Gradually raising the serum sodium with tolvaptan was associated with significant improvement on the Mental Component of the Medical Outcomes Study Short-Form General Health Survey at 30 days. This benefit was significant only in patients with a serum sodium concentration between 120 and 129 mEq/L and was not seen with correction of mild hyponatremia (130 to 134 mEq/L) or in the placebo group. (See "Overview of the treatment of hyponatremia in adults", section on 'Vasopressin receptor antagonists'.)

●A case control study found that older adult patients (mean age 72 years) who presented to an emergency department with falls were significantly more likely to have mild to moderate hyponatremia (serum sodium concentration 120 to 130 mEq/L) than older adult patients who did not experience falls [25]. Serial studies in the same patients suggested improvement in gait when the serum sodium concentration was normal.

●In a case series of 23 older adults with moderate hyponatremia, correction of hyponatremia (usually with urea) improved performance on tests of reaction time and gait; the potential effect was significant among patients older than 65 years but not among younger individuals [26].

●In a randomized crossover trial of 14 older adults with moderate hyponatremia (median serum sodium 131 mEq/L), a rise in serum sodium concentration during treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor improved scoring on a neurocognitive test (Montreal Cognitive Assessment) [27].

Mild to moderate hyponatremia may contribute to fractures in older adult patients [28,29]. In addition to a higher risk of falls, patients with hyponatremia are more likely to have osteoporosis than patients without hyponatremia [29]. The higher prevalence of osteoporosis may be due at least in part to loss of bone sodium. (See "Osteoporotic fracture risk assessment", section on 'Possible risk factors'.)

Hyponatremia, even if mild, is associated with increased mortality in both hospitalized and ambulatory patients [30-35]. The reasons for this association have not been identified, but they could reflect some of the adaptations of several organ systems to hyponatremia that allow them to function at low serum sodium concentrations [23]. Mortality risk in hospitalized patients with hyponatremia is increased across virtually all clinical subgroups and persists after hospital discharge, regardless of the underlying disease [35]. A meta-analysis of 15 studies encompassing 13,816 hyponatremic patients found that an improvement in the serum sodium concentration was associated with a decreased mortality rate [36]. This finding likely resulted from simultaneous improvements in underlying comorbidities, rather than a cause-effect relationship between serum sodium and mortality.

However, the association between serum sodium concentration and mortality in hospitalized patients is nonlinear. Several studies have found that mortality risk increases as serum sodium decreases to approximately 125 mEq/L; below 120 mEq/L, patients have lower rather than higher mortality risk [37-39]. The explanation for this paradox may be that extremely low serum sodium concentrations are most commonly drug induced, whereas mild to moderate hyponatremia is more likely to be associated with a life-threatening underlying disease (malignancy, oliguric kidney failure, heart failure, or hepatic cirrhosis) [37-39]. Similarly, drug-induced hyponatremia tends to resolve spontaneously when the drug is discontinued, while hyponatremia associated with a severe underlying disease tends to persist [38,39].

Hyponatremia, even if mild, is also associated with increased morbidity in hospitalized patients. As an example, in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, the 75,423 patients with preoperative hyponatremia (sodium level of <135 mEq/L) compared with 888,840 patients with normonatremia had significantly higher perioperative 30-day mortality (5.2 versus 1.3 percent), major coronary events (1.8 versus 0.7 percent), wound infection (7.4 versus 4.6 percent), and pneumonia (3.7 versus 1.5 percent) [33].

Susceptibility of premenopausal females — Premenopausal females and young children with acute postoperative hyponatremia may progress rapidly from minimal symptoms (headache and nausea) to respiratory arrest [7,40]. Cerebral edema and herniation have been found at autopsy, leading some authors to suggest a possible hormonally-mediated decrease in the degree of osmotic adaptation [7,41]. The observation that prepubertal children are at equal risk of symptomatic hyponatremia is compatible with the importance of sex hormones in conferring susceptibility to adult females [42]. Other factors may play a role, such as the size of the brain in relationship to the capacity of the cranial vault, and a more rapid onset of hyponatremia because of smaller body size with less muscle to "buffer" the excess water.

Osmotic demyelination — The adaptation that returns the brain volume toward normal in chronic hyponatremia protects against the development of cerebral edema but also creates a potential problem when the serum sodium is therapeutically or spontaneously corrected. In this setting, an overly rapid increase in the serum sodium concentration can lead to an osmotic demyelination syndrome (also called central pontine myelinolysis, although demyelination is often more diffuse and does not necessarily involve the pons). These changes can lead to potentially severe neurologic symptoms that are usually delayed for two to six days after correction and may be irreversible. Thus, patients with symptomatic hyponatremia may initially demonstrate neurologic improvement with correction of the serum sodium but then show late deterioration. This complication of treatment may be reversed by relowering of the serum sodium (figure 2). These issues are discussed in detail elsewhere. (See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia", section on 'Patients who have exceeded correction limits (rescue strategy)' and "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia", section on 'Pathogenesis of ODS'.)

HYPERNATREMIA — Hypernatremia is basically a mirror image of hyponatremia [1,2,4,5,43]. A rise in the serum sodium concentration and osmolality causes water movement out of the brain.

Manifestations of acute hypernatremia — With acute hypernatremia (eg, after the inadvertent infusion of hypertonic saline into a uterine vein during therapeutic abortion, or the ingestion of large amounts of salt) the rapid decrease in brain volume can cause rupture of the cerebral veins, leading to focal intracerebral and subarachnoid hemorrhages and possibly irreversible neurologic damage [1,2,4,44]. Acute hypernatremia can also result in demyelinating brain lesions similar to those associated with overly rapid correction of chronic hyponatremia [45-50]. (See 'Osmotic demyelination' above.)

The clinical manifestations of acute hypernatremia begin with lethargy, weakness, and irritability, and can progress to twitching, seizures, and coma. Severe symptoms usually require an acute elevation in the serum sodium concentration to above 158 mEq/L. Values above 180 mEq/L are associated with a high mortality rate, particularly in adults [51].

Cerebral adaptation to hypernatremia — Beginning on the first day, the initial reduction in brain volume is largely reversed due both to water movement from the cerebrospinal fluid into the brain (thereby increasing the interstitial volume) [5,52] and to the uptake of solutes by the cells (thereby pulling water into the cells and restoring the cell volume) [5,53,54]. The latter response involves an initial uptake of sodium and potassium salts, followed by the later accumulation of osmolytes, which in animals consists primarily of myoinositol, the amino acids glutamine, glutamate, and taurine [53-56]. Myoinositol and taurine are taken up from the extracellular fluid via an increase in the number of sodium-myoinositol and sodium-taurine cotransporters in the cell membrane [54-56]; the source of glutamine and glutamate (uptake from the extracellular fluid or production within the cells) is unknown. The net effect is that these osmolytes, which do not interfere with protein function [18], account for approximately 35 percent of the new cell solute [54].

A report of an infant with an initial serum sodium concentration of 195 mEq/L confirmed the general applicability of these observations to humans [57]. The patient was first studied using proton NMR spectroscopy on day four when the serum sodium concentration had fallen to 156 mEq/L. At this time, there was a 17 mosmol/kg increase in brain osmolyte concentration, due primarily to the accumulation of myoinositol. The excess brain osmolyte concentration fell to 6 mosmol/kg on day 7 and was normal by day 36.

Manifestations of chronic hypernatremia — As in hyponatremia, the cerebral adaptation in hypernatremia has two important clinical consequences:

●Chronic hypernatremia, which is defined as hypernatremia that has been present for more than a day, is much less likely to induce neurologic symptoms. Assessment of symptoms attributable to hypernatremia is often difficult because most affected adults have underlying neurologic disease. The latter is required to diminish the protective thirst mechanism that normally prevents the development of hypernatremia, even in patients with arginine vasopressin disorders (formerly called diabetes insipidus). (See "Etiology and evaluation of hypernatremia in adults".)

Like hyponatremia, hypernatremia, even if mild, is associated with increased morbidity and mortality. A cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) compared 20,029 patients with preoperative hypernatremia (>144 mmol/L) to 888,840 patients with a normal baseline serum sodium (135 to 144 mmol/L) [58]. Preoperative hypernatremia was associated with increased perioperative 30-day mortality (5.2 versus 1.3 percent), perioperative major coronary events (1.6 versus 0.7 percent), pneumonia (3.4 versus 1.5 percent), and venous thromboembolism (1.8 versus 0.9 percent).

In infants, correction of chronic hypernatremia must occur slowly to prevent rapid fluid movement into the brain and cerebral edema, changes that can lead to seizures and coma [59]. Although the brain cells can rapidly lose potassium and sodium in response to cell swelling, the loss of accumulated osmolytes and the water they obligate occurs more slowly [5,54]. The loss of myoinositol, for example, requires both a reduction in the synthesis of new sodium-inositol cotransporters [55] and the activation of a specific inositol efflux mechanism in the cell membrane [60]. The delayed clearance of osmolytes from the cell can predispose to cerebral edema if the serum sodium concentration is lowered too rapidly. As a result, the rate of correction in young children with hypernatremia should be less than 10 to 12 mEq/L per day [61,62].

Rapid correction of hypernatremia has not been shown to have adverse consequences in adults [63-65], and fear of cerebral edema from overly rapid correction of hypernatremia, which has only been reported in infants, should not deter vigorous rehydration of adults with acute hypernatremia who are at risk of developing osmotic demyelination or brain hemorrhage from untreated hypernatremia. Unlike hyponatremia, there is little risk of inadvertent overcorrection in adults with hypernatremia; such patients are often undertreated, and more rapid correction may be beneficial [1,66,67]. As an example, in a retrospective study of 4265 adults with serum sodium concentrations ≥155 mEq/L (most had chronic hypernatremia), patients corrected by >0.5 mEq/L per hour had decreased 30-day mortality compared with those corrected more slowly [65]. Although it is difficult to exclude confounding by comorbidities, there was no evidence of harm from more rapid correction. These findings support vigorous rehydration of adults with hypernatremia regardless of the duration of the disturbance. (See "Treatment of hypernatremia in adults", section on 'Choosing a rate of correction'.)

SENSING OF CHANGES IN PLASMA OSMOLALITY — Although the mechanisms of protective solute loss in hyponatremia and solute uptake in hypernatremia have been largely defined, the mechanisms by which the alterations in plasma osmolality are sensed by the cells (particularly brain cells) and then lead to the physiologically appropriate changes in solute content are not well understood. There is preliminary evidence that hyperosmolality, perhaps via stress on the cytoskeleton as the cell volume falls, activates a specific protein kinase [68]. This kinase, via protein phosphorylation, may then lead to activation of transporters, such as the sodium-inositol cotransporter, that promote solute uptake into the cells.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyponatremia" and "Society guideline links: Fluid and electrolyte disorders in adults".)

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SUMMARY — Symptoms associated with hyponatremia or hypernatremia are primarily neurologic and related to the severity and rapidity of the change in the serum sodium concentration. Such symptoms must be distinguished from those of concurrent volume depletion and possible underlying neurologic diseases that may predispose to the electrolyte abnormality. (See 'Introduction' above.)

●Hyponatremia: Clinical manifestations

•Symptoms directly attributable to hyponatremia reflect neurologic dysfunction induced by cerebral edema. Cerebral edema is due to a decrease in serum osmolality which causes water movement into cells.

•Clinical manifestations of acute hyponatremia reflect the severity of cerebral overhydration. Nausea and malaise are the earliest findings, and may be seen at a serum sodium concentration below 125 to 130 mEq/L. Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest may occur if the serum sodium concentration falls below 115 to 120 mEq/L. Hyponatremic encephalopathy may be reversible or permanent. Premenopausal females appear to be at greater risk for severe hyponatremic symptoms and for residual neurologic injury. (See 'Clinical manifestations of acute hyponatremia' above and 'Susceptibility of premenopausal females' above.)

•Because of the cerebral adaptation, neurologic symptoms are much less severe with chronic hyponatremia. Patients with chronic hyponatremia may appear to be asymptomatic despite a serum sodium concentration that is persistently below 120 mEq/L. Symptoms that do occur include fatigue, nausea, dizziness, gait disturbances, forgetfulness, confusion, lethargy, and muscle cramps. Seizures and coma are uncommon and often reflect an acute exacerbation of the hyponatremia. (See 'Osmolytes and cerebral adaptation to hyponatremia' above and 'Clinical manifestations of chronic hyponatremia' above.)

•Neurologic manifestations resulting from chronic hyponatremia, including gait disturbance and attention deficits, may result in increased falls among older adult patients. Even mild hyponatremia is associated with increased mortality, although the hyponatremia may just be a marker for more severe underlying disease. (See 'Subtle manifestations in mild to moderate chronic hyponatremia' above.)

•An overly rapid increase in the serum sodium concentration can lead to osmotic demyelination syndrome (also called central pontine myelinolysis) resulting in severe and potentially irreversible neurologic symptoms. (See 'Osmotic demyelination' above and "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia", section on 'Pathogenesis of ODS'.)

●Hypernatremia: Clinical manifestations

•Hypernatremia causes water movement out of the brain resulting in a decrease in brain volume that, if acute, can cause focal intracerebral and subarachnoid hemorrhages, demyelinating brain lesions, and irreversible neurologic damage. (See 'Manifestations of acute hypernatremia' above.)

•Hypernatremic patients who become symptomatic present with lethargy, weakness, and irritability, and may develop twitching, seizures, and coma. Severe symptoms usually require an acute elevation in the serum sodium concentration to above 158 mEq/L. Values above 180 mEq/L are associated with a high mortality rate, particularly in adults. (See 'Manifestations of acute hypernatremia' above.)

•Because of the cerebral adaptation, chronic hypernatremia is less likely to induce neurologic symptoms. The correction of chronic hypernatremia must occur slowly to prevent rapid fluid movement into the brain and cerebral edema. The rate of correction in asymptomatic patients should not exceed 12 mEq/L per day, which represents an average of 0.5 mEq/L per hour. (See 'Cerebral adaptation to hypernatremia' above and "Treatment of hypernatremia in adults", section on 'Choosing a rate of correction'.)