Hyponatremia in Emergency Medicine 

Updated: Dec 28, 2018
Author: Kartik Shah, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP 



Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium. Clinically significant hyponatremia is relatively uncommon and is nonspecific in its presentation; therefore, the physician must consider the diagnosis in patients presenting with vague constitutional symptoms or with altered level of consciousness. Irreparable harm can befall the patient when abnormal serum sodium levels are corrected too quickly or too slowly. The physician must have a thorough understanding of the pathophysiology of hyponatremia to initiate safe and effective corrective therapy. The patient's fluid status must be accurately assessed upon presentation, as it guides the approach to correction.[1]

Hypovolemic hyponatremia

Total body water (TBW) decreases; total body sodium (Na+) decreases to a greater extent. The extracellular fluid (ECF) volume is decreased.

Euvolemic hyponatremia

TBW increases while total sodium remains normal. The ECF volume is increased minimally to moderately but without the presence of edema.

Hypervolemic hyponatremia

Total body sodium increases, and TBW increases to a greater extent. The ECF is increased markedly, with the presence of edema.

Redistributive hyponatremia

Water shifts from the intracellular to the extracellular compartment, with a resultant dilution of sodium. The TBW and total body sodium are unchanged. This condition occurs with hyperglycemia or administration of mannitol.


The aqueous phase is diluted by excessive proteins or lipids. The TBW and total body sodium are unchanged. This condition is seen with hypertriglyceridemia and multiple myeloma.


Serum sodium concentration is regulated by stimulation of thirst, secretion of ADH, feedback mechanisms of the renin-angiotensin-aldosterone system, and variations in renal handling of filtered sodium. Increases in serum osmolarity above the normal range (280-300 mOsm/kg) stimulate hypothalamic osmoreceptors, which, in turn, cause an increase in thirst and in circulating levels of ADH. ADH increases free water reabsorption from the urine, yielding urine of low volume and relatively high osmolarity and, as a result, returning serum osmolarity to normal. ADH is also secreted in response to hypovolemia, pain, fear, nausea, and hypoxia.

Aldosterone, synthesized by the adrenal cortex, is regulated primarily by serum potassium but also is released in response to hypovolemia through the renin-angiotensin-aldosterone axis. Aldosterone causes absorption of sodium at the distal renal tubule. Sodium retention obligates free water retention, helping to correct the hypovolemic state. The healthy kidney regulates sodium balance independently of ADH or aldosterone by varying the degree of sodium absorption at the distal tubule. Hypovolemic states, such as hemorrhage or dehydration, prompt increases in sodium absorption in the proximal tubule. Increases in vascular volume suppress tubular sodium reabsorption, resulting in natriuresis and helping to restore normal vascular volume. Generally, disorders of sodium balance can be traced to a disturbance in thirst or water acquisition, ADH, aldosterone, or renal sodium transport.

Hyponatremia is physiologically significant when it indicates a state of extracellular hyposmolarity and a tendency for free water to shift from the vascular space to the intracellular space. Although cellular edema is well tolerated by most tissues, it is not well tolerated within the rigid confines of the bony calvarium. Therefore, clinical manifestations of hyponatremia are related primarily to cerebral edema. The rate of development of hyponatremia plays a critical role in its pathophysiology and subsequent treatment. When serum sodium concentration falls slowly, over a period of several days or weeks, the brain is capable of compensating by extrusion of solutes and fluid to the extracellular space. Compensatory extrusion of solutes reduces the flow of free water into the intracellular space, and symptoms are much milder for a given degree of hyponatremia.

When serum sodium concentration falls rapidly, over a period of 24-48 hours, this compensatory mechanism is overwhelmed and severe cerebral edema may ensue, resulting in brainstem herniation and death.



United States

Hyponatremia is the most common electrolyte disorder, with a marked increase among hospitalized and nursing home patients. A 1985 prospective study of inpatients in a US acute care hospital found an overall incidence of approximately 1% and a prevalence of approximately 2.5%. On the surgical ward, approximately 4.4% of postoperative patients developed hyponatremia within 1 week of surgery. Hyponatremia has also been observed in approximately 30% of patients treated in the intensive care unit.[2]


Though clearly not indicative of the overall prevalence internationally, hyponatremia has been observed in up to 42.6% of patients in a large acute care hospital in Singapore and in 30% of patients hospitalized in an acute care setting in Rotterdam.[3, 4]


Pathophysiologic differences between patients with acute and chronic hyponatremia engender important differences in their morbidity and mortality.

Patients with acute hyponatremia (developing over 48 h or less) are subject to more severe degrees of cerebral edema for a given serum sodium level. The primary cause of morbidity and death is brainstem herniation and mechanical compression of vital midbrain structures. Rapid identification and correction of serum sodium level is necessary in patients with severe acute hyponatremia to avert brainstem herniation and death.

Patients with chronic hyponatremia (developing over more than 48 h) experience milder degrees of cerebral edema for a given serum sodium level. Brainstem herniation has not been observed in patients with chronic hyponatremia. The principal direct causes of morbidity and death are status epilepticus (when chronic hyponatremia reaches levels of 110 mEq/L or less) and cerebral pontine myelinolysis (an unusual demyelination syndrome that occurs in association with chronic hyponatremia and its rapid correction).

The distinction between acute hyponatremia and chronic hyponatremia has critical implications in terms of morbidity and mortality and in terms of proper corrective therapy.

A study of 98,411 hospitalized patients found that even mild degrees of hyponatremia were associated with increased inhospital, 1-year and 5-year mortality rates. Mortality was particularly increased in those with cardiovascular disease, metastatic cancer, and those undergoing orthopedic procedures.[5]

Similarly, a study by McCarthy et al found that patients with lower sodium levels at emergency admission tended to have a longer hospital stay than did those with normal sodium concentrations (6.8 vs 4.9 days, respectively), with the hyponatremic patients also having a higher 30-day inhospital mortality rate (6.4% vs 4.4%, respectively).[6]

A study in Copenhagen concluded that hyponatremia in the range of 130-137 mEq/L is also associated with increased mortality rates in the general population.[7]


Overall incidence of hyponatremia is approximately equal in males and females, though postoperative hyponatremia appears to be more common in menstruant females.


Hyponatremia is most common in the extremes of age; these groups are less able to experience and express thirst and less able to regulate fluid intake autonomously. Specific settings that have been known to pose particular risk include the following:

  • Infants fed tap water in an effort to treat symptoms of gastroenteritis

  • Infants fed dilute formula in attempt to ration

  • Elderly patients with diminished sense of thirst, especially when physical infirmity limits independent access to food and drink[8, 9]


Prognosis is dependent on the underlying condition and the severity of disease.




The number and severity of symptoms increase with the degree of hyponatremia and the rapidity with which it develops. When the serum sodium level falls gradually, over a period of several days or weeks, sodium levels as low as 110 mEq/L may be reached with minimal symptomatology. In contrast, an equivalent fall in serum sodium level over 24-48 hours may overwhelm compensatory mechanisms, leading to severe cerebral edema, coma, or brainstem herniation.

Symptoms range from mild anorexia, headache, and muscle cramps, to significant alteration in mental status including confusion, obtundation, coma, or status epilepticus.

Hyponatremia is often seen in association with pulmonary/mediastinal disease or CNS disorders. Hyponatremia must be considered in patients with pneumonia, active tuberculosis, pulmonary abscess, neoplasm, or asthma, as well as in patients with CNS infection, trauma, or neoplasm. Patients with carcinoma of the nasopharynx, duodenum, stomach, pancreas, ureter, prostate, or uterus also have an increased risk.

Hyponatremia is associated with numerous medications. The patient's medication list should be examined for drugs known to cause hyponatremia.

Hyponatremia has been noted in patients with poor dietary intake who consume large amounts of beer (known as beer potomania) and after use of the recreational drug N- methyl-3,4-methylenedioxyamphetamine (ie, MDMA or ecstasy). MDMA-induced hyponatremia occurs via multiple mechanisms; these include the induction of syndrome of inappropriate antidiuretic hormone secretion (SIADH), the encouragement to drink large amounts of water to prevent unpleasant side effects of the drug, and the tendency among those intoxicated to be involved in vigorous physical activity that results in heavy sweating.

A history of hypothyroidism or adrenal insufficiency should be sought because each is associated with hyposmolar hyponatremia.

Patients with clinically significant hyponatremia present with nonspecific symptoms attributable to cerebral edema. These symptoms, especially when coupled with a recent history of altered fluid balance, should suggest the possibility of hyponatremia.

  • Anorexia

  • Nausea and vomiting

  • Difficulty concentrating

  • Confusion

  • Lethargy

  • Agitation

  • Headache

  • Seizures


Physical findings are highly variable and dependent on the degree and the chronicity of hyponatremia. Patients with acutely developing hyponatremia are typically symptomatic at a level of approximately 120 mEq/L. Those patients with chronic hyponatremia tolerate much lower levels.

Most abnormal findings on physical examination are neurologic in origin.

  • Level of alertness ranging from alert to comatose

  • Variable degrees of cognitive impairment (eg, difficulty with short-term recall; loss of orientation to person, place, or time; frank confusion or depression)

  • Focal or generalized seizure activity

  • In those patients with acute severe hyponatremia, signs of brainstem herniation, including coma; fixed, unilateral, dilated pupil; decorticate or decerebrate posturing; sudden severe hypertension and respiratory arrest

In addition to neurologic findings, patients may exhibit signs of hypovolemia or hypervolemia. Determining the hydration status of the patient may help establish the etiology of the hyponatremia and direct subsequent treatment.

  • Dry mucous membranes, tachycardia, diminished skin turgor, and orthostasis suggest hypovolemic hyponatremia due to excessive loss of body fluids and replacement with inappropriately dilute fluids.

  • Pulmonary rales, S3 gallop, jugular venous distention, peripheral edema, or ascites suggest hypervolemic hyponatremia due to excess retention of sodium and free water (ie, cirrhosis, nephrotic syndrome, congestive heart failure).

  • Patients who lack findings of hypovolemia or hypervolemia are considered to have euvolemic hyponatremia, which is consistent with such etiologies as exogenous free water load, hypothyroidism, cortisol deficiency, or SIADH.

Other nonspecific signs include muscle weakness and cramping. Rhabdomyolysis is an occasional consequence of hyponatremia and should be considered in patients with muscle pain or tenderness.


Hypovolemic hyponatremia develops as sodium and free water are lost and replaced by inappropriately hypotonic fluids, such as tap water, half-normal saline, or dextrose in water. Sodium can be lost through renal or nonrenal routes. Nonrenal routes include GI losses, excessive sweating, third spacing of fluids (eg, ascites, peritonitis, pancreatitis, burns), and cerebral salt-wasting syndrome.

  • Excess fluid losses (eg, vomiting, diarrhea, excessive sweating, GI fistulas or drainage tubes, pancreatitis, burns) that have been replaced primarily by hypotonic fluids
  • Salt-wasting nephropathy

Cerebral salt-wasting syndrome seen in patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracranial surgery. Cerebral salt-wasting must be distinguished from SIADH because both conditions can cause hyponatremia in neurosurgical patients, and yet the pathophysiology and treatment are different.[10]

Prolonged exercise in a hot environment, especially in patients who hydrate aggressively with hyposmolar fluids during exertion, is another cause of hyponatremia. Severe symptomatic hyponatremia has been reported in marathon runners and in recreational hikers in the Grand Canyon.

A study by Giordano et al found a significant increase in the prevalence of hyponatremia in elderly patients visiting a university hospital emergency department during the summer. Prevalence during the summer was 12.5% (zenith) in the elderly, compared with a mean monthly prevalence of 10.3% in these patients. The investigators suggested that factors such as reduced renal function, salt loss, a decline in salt intake, and increased water ingestion may play a role in the increased prevalence of hyponatremia in the elderly during hot-weather months.[11]

Similarly, a study by Huwyler et al found an increased incidence of adult patients with profound hyponatremia in a university hospital emergency department during the summer (1.29%, compared with 0.54% in the winter). Based on multivariate analysis, the investigators reported that the rise in incidence was related to patient age, the presence of psychiatric disorders, and the use of diuretics (either potassium-sparing or thiazide).[12]

Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. This occurs in patients who take in excess hypotonic fluids.

  • Psychogenic polydipsia, often in psychiatric patients

  • Administration of hypotonic intravenous or irrigation fluids during procedures or in the immediate postoperative period[13, 14]

  • In one meta-analysis, administration of hypotonic maintenance intravenous fluids to hospitalized children has been associated with an increased incidence of acute hyponatremia compared with administration of isotonic maintenance fluids.[15]

  • Infants who may have been given inappropriate amounts of free water

  • Ingestion of sodium phosphate or sodium picosulfates and magnesium citrate combination as a bowel preparation before colonoscopy or colorectal surgery[16]


Hypervolemic hyponatremia occurs when sodium stores increase inappropriately. This may result from renal causes such as acute or chronic renal failure, when dysfunctional kidneys are unable to excrete the ingested sodium load. It also may occur in response to states of decreased effective intravascular volume. History of hepatic cirrhosis, congestive heart failure, or nephrotic syndrome, in which patients are subject to insidious increases in total body sodium and free water stores

  • Uncorrected hypothyroidism or cortisol deficiency (adrenal insufficiency, hypopituitarism)

  • Consumption of large quantities of beer or use of the recreational drug MDMA (ecstasy)

Hyponatremia can be caused by many medications. Known offenders include acetazolamide, amiloride, amphotericin, aripiprazole, atovaquone, thiazide diuretics, amiodarone, basiliximab, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, bromocriptine, carbamazepine, carboplatin, carvedilol, celecoxib, cyclophosphamide, clofibrate, desmopressin, donepezil, duloxetine, eplerenone, gabapentin, haloperidol, heparin, hydroxyurea, indapamide, indomethacin, ketorolac, levetiracetam, loop diuretics, lorcainide, mirtazapine, mitoxantrone, nimodipine, oxcarbazepine, opiates, oxytocin, pimozide, propafenone, proton pump inhibitors, quetiapine, sirolimus, ticlopidine, tolterodine, vincristine, selective serotonin reuptake inhibitors, sulfonylureas, trazodone, tolbutamide, venlafaxine, zalcitabine, and zonisamide.[17]

A study by Poddighe of 328 pediatric emergency department patients indicated that a systemic inflammatory condition is associated with mild hyponatremia during acute illnesses, finding, in the 98 patients determined to have (mostly mild) hyponatremia, a link between lower plasma sodium levels and higher levels of C-reactive protein.[18]

Overall, the above causes are not mutually exclusive, with hyponatremia often resulting from multiple factors.[19]


Complications related to hyponatremia include rhabdomyolysis, seizures, permanent neurologic sequelae related to ongoing seizures or cerebral edema, respiratory arrest, and death.

A retrospective study by Brouns et al indicated that among elderly internal medicine patients presenting to the emergency department, hyponatremia is a risk factor for hospital admission, longer hospital stay, and 3-month mortality, with moderate hyponatremia being particularly associated with frailty and mortality. In a comparison of hyponatremic elderly patients with those who did not have clinically relevant hyponatremia, admission rates were 93.4% versus 72.9%, respectively; hospital stay was 8 days versus 6 days, respectively; and 3-month survival rate was 74% versus 83%, respectively.[20]

Complications related to therapy of hyponatremia include fluid overload and the osmotic demyelination syndrome.





Laboratory Studies

The diagnosis of hyponatremia depends entirely on the ability to properly obtain a sample of the patient's serum and to accurately measure its concentration of sodium.

When interpreting serum sodium levels, always consider the possibility of sampling error, especially when the reported value does not seem consistent with the history or physical findings.

  • Was the patient's blood sample properly labeled?

  • Was it obtained from a venous site proximal to an infusion of hypotonic saline or dextrose in water?

  • Is laboratory measurement or reporting in error?

  • If an error is suspected, a second sample should be submitted for testing before therapeutic measures are initiated.

In addition to sampling and analysis errors, several physiologic states exist in which correct laboratory analysis yields low serum sodium levels, but these levels do not reflect a true hyposmolar state.

The most common example is serum hyperglycemia. Accumulation of extracellular glucose induces a shift of free water from the intracellular space to the extracellular space. Serum sodium concentration is diluted by a factor of 1.6 mEq/L for each 100 mg/dL increase above normal serum glucose concentration. Systemic osmolarity is normal or even increased, not decreased, as in true (ie, hyposmolar) hyponatremia. This hypertonic hyponatremia has no physiologic significance, and serum sodium concentration corrects as normoglycemia is reestablished.

A similar phenomenon is observed in patients treated with glycerol or mannitol in an effort to control acute glaucoma or intracranial hypertension. This phenomenon is also seen in patients with advanced renal disease who receive radiocontrast agents for diagnostic testing.

Hyponatremia may be noted in patients whose serum contains unusually large quantities of protein or lipid. In these patients, an expanded plasma protein or lipid fraction leads to a decrease in the plasma water fraction in which sodium is dissolved. Laboratory techniques that measure absolute sodium content per unit of plasma water report low sodium levels despite the fact that the concentration of sodium in serum water remains within the normal range. This phenomenon, known as pseudohyponatremia, occurs when flame emission spectrophotometry or indirect potentiometry is used to assay serum sodium levels rather than direct potentiometry techniques. This occurs in approximately 60% of US laboratories.

Serum osmolarity remains undisturbed, and attempts at correcting serum sodium level are not indicated. Hyperlipidemia that is severe enough to produce pseudohyponatremia almost always is accompanied by a notably lipemic appearance of the serum sample. Hyperproteinemia of sufficient magnitude to induce pseudohyponatremia commonly is due to coexisting multiple myeloma.

Serum osmolarity is helpful in establishing the diagnosis of true hyposmolar hyponatremia. Serum osmolarity is abnormally low in patients with hyposmolar hyponatremia, but it is normal in patients with pseudohyponatremia due to hyperlipidemia or hyperproteinemia and normal or elevated in patients with hypertonic hyponatremia due to serum hyperglycemia.

Urine sodium levels are helpful in distinguishing renal causes of hyponatremia from nonrenal causes.

Patients with hypovolemic hyponatremia due to nonrenal causes (eg, vomiting, diarrhea, fistulas, GI drainage, third spacing of fluids) have avid renal absorption of tubular sodium and urine sodium levels of less than 20 mEq/L, whereas those with hypovolemic hyponatremia due to renal causes (eg, diuretics, salt-losing nephropathy, aldosterone deficiency) have inappropriately elevated urine sodium levels in excess of 20 mEq/L.

Patients with hypervolemic hyponatremia due to decreases in effective circulating volume (eg, cirrhosis, nephrosis, congestive heart failure) have urine sodium levels of less than 20 mEq/L, whereas those with renal causes of hypervolemic hyponatremia or with SIADH have urine sodium levels in excess of 20 mEq/L.

Urine osmolarity may be helpful in establishing the diagnosis of SIADH. Typically, patients with SIADH have inappropriately concentrated urine, with urine osmolarities in excess of 100 mOsm/L. Patients with other forms of hyponatremia and appropriately depressed levels of ADH have urine osmolarities below 100 mOsm/L.

Serum thyroid-stimulating hormone (TSH) and free thyroxine levels should be checked if the clinical presentation is consistent with hypothyroidism.

Adrenal function should be assessed, via random serum cortisol levels or adrenocorticotropic hormone (ACTH) stimulation test, in patients who have recently taken oral steroids or in any patient suspected of having cortisol deficiency.

Serum ADH levels are not routinely used in the evaluation of hyponatremia because the assay is technically difficult and not widely available on a stat basis. A serum peptide known as copeptin has been studied in the evaluation of hyponatremia. Copeptin is the C terminal portion of provasopressin and is released in equimolar amounts with vasopressin (ADH). Early research suggested that copeptin might be valuable in the differential diagnosis of hyponatremia, but subsequent studies cast doubt on the additional utility copeptin provides beyond the urine and serum assays already routinely used, especially in the initial approach to hyponatremia in the emergency department.[21, 22]

Imaging Studies

Imaging studies may be indicated depending on the underlying etiology of the hyponatremia (eg, chest radiograph in a patient with congestive heart failure).

Usually, a head CT scan is indicated in the patient with altered mental status to ensure that no other underlying cause for the mental status is present.



Prehospital Care

Hyponatremia is necessarily a hospital-based diagnosis, but patients may exhibit signs of severe neurologic dysfunction during prehospital evaluation and transport.

Address acute life-threatening conditions and initiate supportive care.

Establish reliable intravenous access and give supplemental oxygen to patients with lethargy or obtundation. In these patients, evaluate the possibility of hypoglycemia with a rapid glucose check. Administer intravenous glucose to hypoglycemic patients.

Administer standard prehospital anticonvulsant therapy to patients experiencing seizures. Seizures secondary to hyponatremia are unlikely to respond to this therapy, but it should be administered until a definitive diagnosis and therapy are available.

Intubate and initiate hyperventilation to reduce intracranial pressure in patients exhibiting signs of brainstem herniation (eg, obtundation; fixed, unilateral, dilated pupil; decerebrate or decorticate posturing) until a more definitive therapy can be initiated.

Avoid giving hypotonic intravenous fluids because they may exacerbate cerebral edema.

Emergency Department Care

The ED evaluation of patients with hyponatremia includes determining the cause and the chronicity of the hyponatremic state in order to direct appropriate therapy.[23]

Acute hyponatremia is less common than chronic hyponatremia and typically is seen in patients with a history of sudden free water loading (eg, patients with psychogenic polydipsia, infants fed tap water or inappropriately diluted formula for 1-2 d, patients given hypotonic fluids in the postoperative period, a marathon runner drinking water without electrolyte supplementation).

Acute evolution of hyponatremia leaves little opportunity for compensatory extrusion of CNS intracellular solutes.

The ultimate danger for these patients is brainstem herniation when sodium levels fall below 120 mEq/L.

The therapeutic goal is to increase the serum sodium level rapidly by 4-6 mEq/L over the first 1-2 hours.

The source of free water must be identified and eliminated.

In patients with healthy renal function and mild to moderately severe symptoms, the serum sodium level may correct spontaneously without further intervention.

Patients with seizures, severe confusion, coma, or signs of brainstem herniation should receive hypertonic (3%) saline to rapidly correct serum sodium level toward normal but only enough to arrest the progression of symptoms. An increase in serum sodium level of 4-6 mEq/L is generally sufficient. Any further correction is potentially dangerous and must be avoided unless necessary to correct continued seizures or other severe CNS abnormality. If hypertonic saline is not available, 8.4% sodium bicarbonate can be considered as an alternative for emergent sodium correction.

A Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference provides the following guidelines for exercise-associated hyponatremia:[24, 25]

  • Any athlete with exercise-associated hyponatremia (EAH) associated with signs or symptoms of encephalopathy should be immediately treated with an IV bolus or infusion of hypertonic saline (HTS) to acutely reduce brain edema, with additional IV boluses administered until there is clinical improvement.
  • The dose and route of HTS administration should be based upon the severity of clinical symptoms and the available HTS formulations.
  • The goal of IV HTS therapy is to stabilize the athlete for transfer to an advanced medical care facility.
  • The use of IV HTS as the definitive treatment for acute hyponatremic encephalopathy is well validated, with the IV HTS bolus able to increase serum sodium levels 2-5 mmol/L, which decreases intracranial pressure and reduces symptoms.
  • If the diagnosis of EAH is not confirmed, administration of HTS in small boluses is not associated with any negative consequences and serves as an excellent volume expander.

Chronic hyponatremia is more common than acute hyponatremia. Patients with mild symptoms and a serum sodium level of 125 mEq/L or less often have chronic hyponatremia. These patients lack any history of sudden free water loading.

Chronic hyponatremia must be managed with extreme care. Treatment of chronic hyponatremia has been associated with the development of the osmotic demyelination syndrome (also known as central pontine myelinolysis) characterized by focal demyelination in the pons and extrapontine areas associated with serious neurologic sequelae.

The pathophysiology of osmotic demyelination is controversial. Multiple cohort studies and 3 reviews of the literature suggest that the syndrome is caused by overly rapid correction or overcorrection of chronic hyponatremia.[26] Some investigators note that osmotic demyelination often develops when chronic hyponatremia is complicated by hypoxia and believe that osmotic demyelination may be a form of hypoxic encephalopathy associated with hyponatremia and not a complication of therapy.[27] Until further data are available, management should include meticulous attention to adequate oxygenation and a gradual increase in serum sodium level to 120-125 mEq/L. Serum sodium level should not be allowed to reach normal levels or hypernatremic levels within the first 48 hours.

Symptoms of osmotic demyelination (eg, dysarthria, dysphagia, seizures, altered mental status, quadriparesis, hypotension) typically begin 1-5 days after correction of serum sodium level.[28]

The condition is typically irreversible and often devastating. Slow, cautious correction of serum sodium level and maintenance of adequate oxygenation in these patients is important.

Patients with hypokalemia, female gender, or history of alcoholism or liver transplant seem to be particularly prone to develop osmotic demyelination.[29] Exercise extreme caution in treating hyponatremia in these subgroups.

To minimize the risk of osmotic demyelination, older literature recommended correction of sodium in chronic hyponatremia at a rate no greater than 10-12 mEq/L in the first 24 hours. However, newer guidelines recommend a maximum of 8 mEq/L in the first 24 hours, with a maximum of 6 mEq/L for patients at high risk of osmotic demyelination. The authors will use the safer margin as our recommendation.[26]

Patients with chronic hyponatremia and severe symptoms (eg, severe confusion, coma, seizures) should receive hypertonic saline but only enough to raise the serum sodium level by 4-6 mEq/L and to arrest seizure activity. After this, we recommend no further correction of the sodium for the first 24 hours. Reports suggest that therapeutic relowering of the serum sodium level with hypotonic fluids and desmopressin (DDAVP) may help avert neurologic sequelae in patients whose chronic hyponatremia is inadvertently corrected too quickly.[30]

In treating patients with chronic hyponatremia and mild to moderately severe symptoms, consider the cause of the hyponatremic state. Patients are classified as having hypovolemic, euvolemic, or hypervolemic hyponatremia based on historical clues and physical examination. Regardless of the therapeutic approach, serum sodium must be monitored closely and corrected no faster than 6 mEq/L in the first 24 hours.

Patients with hypovolemic hyponatremia who are hypotensive and have signs of decreased end-organ perfusion may need IV fluid volume repletion in addition to sodium correction. Careful treatment with isotonic saline may be considered, but monitor serum sodium levels frequently to ensure that the serum sodium level increases slowly, with a maximum rise of 6 mEq/L in the first 24 hours. Be aware that as isotonic saline is given, large-volume diuresis of dilute urine may occur, causing overcorrection of sodium. As such, some practitioners will give low-dose (1-2 μg) DDAVP, continued every 6-8 hours, before administering IV fluids, thereby proactively decreasing urine output and preventing the overcorrection of sodium.[19, 31]

Patients with hypervolemic hyponatremia have increased total body sodium stores. Treatment consists of sodium and water restriction and attention to the underlying cause. The vasopressin receptor antagonists conivaptan (Vaprisol) and tolvaptan (Samsca) are now approved for use in hospitalized patients with hypervolemic hyponatremia, though clinical experience is scant.[32]

In April 2013, the FDA limited use of tolvaptan to no more than 30 days and indicated that it should not be used in patients with underlying liver disease. This decision was based on reports of liver injury, including those potentially leading to liver transplant or death.[33]

Euvolemic hyponatremia implies normal sodium stores and a total body excess of free water. Treatment consists of free water restriction and correction of the underlying condition. Recently developed AVP (vasopressin) receptor antagonists (eg, conivaptan, tolvaptan) show promise as effective and well-tolerated intravenous therapy for SIADH. Further studies are needed to better define their role in the treatment of hyponatremia associated with SIADH.[34]

Special consideration must be given to patients with concomitant hypokalemia and hyponatremia. With potassium repletion, intracellular shifts cause plasma sodium to increase. Consequently, the potassium repletion must be taken into account as patients undergo hypertonic saline therapy, and appropriate downward adjustment of the hypertonic saline dosage should be made.[35]

Medical Care

Admit patients with severely symptomatic hyponatremia manifested by coma, recurrent seizures, or evidence of brainstem dysfunction to an ICU and monitor serum sodium levels closely.

Admit patients with a propensity toward inappropriate free water ingestion to a unit where free water access is restricted. Clozapine appears to be effective in the long-term treatment of schizophrenic patients with compulsive water drinking.

Discontinue medications known to be associated with hyponatremia. Thiazide diuretics are a well-known cause of profound hyponatremia, especially in elderly patients, and should be discontinued in all admitted patients.



Medication Summary

Appropriate treatment of hyponatremia depends on the correct classification of hyponatremia, the concomitant disease state, the severity of symptoms, and the severity of hyponatremia.

Electrolyte Supplements

Class Summary

Hypertonic saline may be used to rapidly increase serum sodium level in patients with severe acute or chronic hyponatremia, as manifested by severe confusion, coma, seizures, or evidence of brainstem herniation.

Hypertonic (3%) saline

Contains 513 mEq/L of NaCl. Volume of hypertonic saline administered depends on current and desired serum sodium levels and patient's weight. In general, increase of 4-6 mEq/L in serum sodium level is sufficient to arrest progression of symptoms in severe hyponatremia. Further rapid increase in serum sodium level not indicated.

Sodium bicarbonate

Commonly available ampoules are 8.4% sodium bicarbonate, with 1 ampoule containing 50 mEq of Na. This can be used to raise serum Na in an emergent scenario where 3% hypertonic saline is not readily available, such as a hyponatremic seizure. For comparison, 100 mL of 3% hypertonic saline contains 51.3 mEq of NaCl.

Arginine Vasopressin Antagonists

Class Summary

These agents treat hyponatremia through V2 antagonism of AVP in the renal collecting ducts. This effect results in aquaresis (excretion of free water).

Conivaptan (Vaprisol)

Arginine vasopressin antagonist (V1A, V2) indicated for euvolemic (dilutional) and hypervolemic hyponatremia. Increases urine output of mostly free water, with little electrolyte loss.

Tolvaptan (Samsca)

Selective vasopressin V2 -receptor antagonist. Indicated for hypervolemic and euvolemic hyponatremia (ie, serum sodium level < 125 mEq/L) or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction. Used for hyponatremia associated with congestive heart failure, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion. Initiate or reinitiate in hospital environment only. Duration of use is limited to 30 days to minimize risk of liver injury.


Questions & Answers


What is hyponatremia?

What is hypovolemic hyponatremia?

What is euvolemic hyponatremia?

What is the hypervolemic hyponatremia?

What is redistributive hyponatremia?

What is pseudohyponatremia?

What is the pathophysiology of hyponatremia?

What is the prevalence of hyponatremia in the US?

What is the global prevalence of hyponatremia internationally?

What are the mortality and morbidity associated with hyponatremia?

What are the sexual predilections of hyponatremia by gender?

Which age groups have the highest prevalence of hyponatremia?

What is the prognosis of hyponatremia?


Which clinical history findings are characteristic of hyponatremia?

What are the symptoms of hyponatremia?

Which neurologic findings are characteristic of hyponatremia?

Which nonneurologic findings are characteristic of hyponatremia?

What causes hyponatremia?

Why is hyponatremia more present in the summer months?

What causes euvolemic hyponatremia?

What causes hypervolemic hyponatremia?

Which medications cause hyponatremia, and are the causes of hyponatremia multifactorial?

What are the possible complications of hyponatremia?


What are the differential diagnoses for Hyponatremia in Emergency Medicine?


How is hyponatremia diagnosed?

What causes sampling errors in the diagnosis of hyponatremia?

Which physiologic states with low serum sodium levels are not hyponatremic?

What is the role of serum osmolarity in the diagnosis of hyponatremia?

What is the role of urine sodium measurement in the diagnosis of hyponatremia?

What is the role of urine osmolarity in the workup of hyponatremia?

What is the role of thyroid testing in the workup of hyponatremia?

What is the role of adrenal function testing in the workup of hyponatremia?

What is the role of serum ADH measurement in the workup of hyponatremia?

What is the role of imaging studies in the workup of hyponatremia?


What is included in the prehospital care of hyponatremia?

How is hyponatremia evaluated and managed in the emergency department (ED)?

What are the Third International Exercise-Associated Hyponatremia Consensus Development Conference guidelines for exercise-associated hyponatremia?

What is chronic hyponatremia?

What is osmotic demyelination in hyponatremia and how is it treated?

What is included in the emergency department (ED) care of severe symptoms of chronic hyponatremia?

How is euvolemic hyponatremia treated, and how is concomitant hypokalemia and hyponatremia addressed?

What is included in the inpatient care of hyponatremia?


Which factors determine treatment selection for hyponatremia?

Which medications in the drug class Arginine Vasopressin Antagonists are used in the treatment of Hyponatremia in Emergency Medicine?

Which medications in the drug class Electrolyte Supplements are used in the treatment of Hyponatremia in Emergency Medicine?