Hyponatremia Treatment & Management

Updated: Jul 16, 2021
  • Author: Eric E Simon, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Approach Considerations

The recommendations for treatment of hyponatremia rely on the current understanding of the central nervous system (CNS) adaptation to an alteration in serum osmolality. In the setting of an acute fall in the serum osmolality, neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space (ie, Starling forces). Therefore, correction of hyponatremia should take into account the limited capacity of this adaptation mechanism to respond to acute alteration in the serum tonicity, because the degree of brain edema and consequent neurologic symptoms depend as much on the rate and duration of hypotonicity as they do on its magnitude.

A panel of United States experts on hyponatremia issued guidelines on the diagnosis, evaluation, and treatment of hyponatremia in 2007; the guidelines were updated in 2013. [35] For treatment of symptomatic patients with acute hyponatremia (ie, with a known duration of < 24-48 hours), the panel recommended urgent correction by 4-6 mmol/L to prevent brain herniation and neurological damage from cerebral ischemia. Recommended treatment of acute hyponatremia varies by symptom severity, as follows:

  • Severe symptoms: 100 mL of 3% NaCl infused intravenously over 10 minutes × 3 as needed
  • Mild to moderate symptoms, in patients at low risk for herniation: 3% NaCl infused at 0.5–2 mL/kg/h

To avoid osmotic demyelination syndrome (ODS) in patients with chronic hyponatremia (known duration > 48 hours), the recommendations include the following [35] :

  • Minimum correction of serum sodium by 4-8 mmol/L per day, with a lower goal of 4-6 mmol/L per day if the risk of ODS is high
  • For patients at high risk of ODS: maximum correction of 8 mmol/L in any 24-hour period
  •  For patients at normal risk of ODS: maximum correction of 10-12 mmol/L in any 24-hour period; 18 mmol/L in any 48-hour period

For patients with the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH), fluid restriction (with a goal of 500 mL/d below the 24-hour urine volume) is generally first-line therapy, but pharmacologic treatment should be strongly considered if the patient's urinary parameters indicate low renal electrolyte-free water excretion or if the serum sodium concentration does not correct after 24-48 hours of fluid restriction. Pharmacologic options include demeclocycline (off label use), urea, and vasopressin receptor antagonists (vaptans). Vaptans should not be used in hypovolemic hyponatremia, or in conjunction with other treatments for hyponatremia. [35]

The European Society of Intensive Care Medicine, the European Society of Endocrinology, and the European Renal Association–European Dialysis and Transplant Association have released guidelines on the diagnosis, classification, and treatment of true hypotonic hyponatremia. Treatment recommendations include the following [3] :

  • For serious symptomatic hyponatremia, the first line of treatment is prompt intravenous infusion of hypertonic saline, with a target increase of 6 mmol/L over 24 hours (not exceeding 12 mmol/L) and an additional 8 mmol/L during every 24 hours thereafter until the patient’s serum sodium concentration reaches 130 mmol/L
  • First-line treatment for patients with SIADH and moderate or profound hyponatremia should be fluid restriction; second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day of urea or combined treatment with low-dose loop diuretics and oral sodium chloride
  • For patients with reduced circulating volume, extracellular volume should be restored with an intravenous infusion of 0.9% saline or a balanced crystalloid solution at 0.5 to 1.0 mL/kg per hour
  • Lithium, demeclocycline, and vaptans are not recommended for patients with moderate or profound hyponatremia

Consultation with either a nephrologist or a critical care specialist is often of considerable value in managing patients with symptomatic or refractory hyponatremia.


Medical Care

Intravenous fluids and water restriction

When faced with a patient with hyponatremia, the first decision is what type of fluid, if any, should be given. The treatment of hypertonic and pseudohyponatremia is directed at the underlying disorder in the absence of symptoms.

Hypotonic hyponatremia accounts for most clinical cases of hyponatremia. The first step in the approach and evaluation of hypotonic hyponatremia is to determine whether emergency therapy is warranted. The following three factors guide treatment:

  • Patient's volume status
  • Duration and magnitude of the hyponatremia
  • Degree and severity of clinical symptoms

For the asymptomatic patient, the following treatments may be of use:

  • Hypovolemic hyponatremia: Administer isotonic saline to patients who are hypovolemic to replace the contracted intravascular volume (thereby treating the cause of vasopressin release). Patients with hypovolemia secondary to diuretics may also need potassium repletion, which, like sodium, is osmotically active. Correction of volume repletion turns off the stimulus to ADH secretion, so a large water diuresis may ensue, leading to a more rapid correction of hyponatremia than desired. If so, hypotonic fluid such as D5/½ normal saline may need to be administered (see below under normovolemic hyponatremia for guidelines).

  • Hypervolemic hyponatremia: Treat patients who are hypervolemic with salt and fluid restriction, plus loop diuretics, and correction of the underlying condition. The use of a V2 receptor antagonist may be considered (see below).

For normovolemic (euvolemic), asymptomatic hyponatremic patients, free water restriction (< 1 L/d) is generally the treatment of choice. There is no role for hypertonic saline in these patients. Base the volume of restriction on the patient's renal diluting capacity. For instance, fluid restriction to 1 L/d, which is enough to raise the serum sodium in some patients, may exceed the renal free water excretion capacity in others, necessitating more severe restriction. This approach is recommended as initial treatment for patients with asymptomatic SIADH. However, many patients will not adhere to fluid restriction. Further, the definition of asymptomatic is changing due to the recognition that subtle but significant deficits, such as in gait, may be present. Therefore, pharmacologic treatment may be considered (see below).

When treating patients with overtly symptomatic hyponatremia (eg, seizures, severe neurological deficits), hypertonic (3%) saline should be used. There is no place in the initial treatment for aquaretics (see below). Note that normal saline can exacerbate hyponatremia in patients with SIADH, who may excrete the sodium and retain the water. A liter of normal (0.9%) saline contains 154 mEq sodium chloride (NaCl) and 3% saline has 513 mEq NaCl. Management decisions should also factor in ongoing renal free water and solute losses.

Alternatively, the combination of intravenous normal saline and diuresis with a loop diuretic (eg, furosemide) also elevates the serum sodium concentration. This latter approach is often useful for patients with high urine osmolality, because the loop diuretic acts to reduce urine osmolality. Concomitant use of loop diuretics increases free water excretion and decreases the risk of fluid overload.

The following equation helps to estimate an expected change in serum sodium (Na) with respect to characteristics of infusates used [36] : Change in serum Na = [(infusate Na + infusate K) - serum Na] / [Total body water +1]

During therapy, close monitoring of serum electrolytes (ie, every 2-4 h) to avoid overcorrection is essential.

Acute hyponatremia (duration < 48 h) can be safely corrected more quickly than chronic hyponatremia. A severely symptomatic patient with acute hyponatremia is in danger from brain edema. In contrast, a symptomatic patient with chronic hyponatremia is more at risk from rapid correction of hyponatremia. Overly rapid correction of serum sodium can precipitate severe neurologic complications, such as central pontine myelinosis, which can produce spastic quadriparesis, swallowing dysfunction, pseudobulbar palsy, and mutism. A symptomatic patient with unknown duration of hyponatremia is the most challenging, warranting a prompt but controlled and limited correction of hyponatremia, until symptoms resolve. However,  fear of osmotic demyelination should not deter prompt and definitive treatment.

With patients who are acutely symptomatic (duration < 48 h, such as after surgery), the treatment goal is to increase the serum sodium level by approximately 1-2 mEq/L/h for 3-4 hours, until the neurologic symptoms subside or until plasma sodium concentration is over 120 mEq/L. [37] Other authors recommend an even more rapid correction. [5]

In chronic, severe symptomatic hyponatremia, the rate of correction should not exceed 0.5-1 mEq/L/h, with a total increase not to exceed 8-12 mEq/L/d and no more than 18 mEq/L in the first 48 h. The sodium concentration must be corrected to a safe range (usually to no greater than 120 mEq/L) rather than to a normal value. As noted above, spontaneous diuresis secondary to ADH suppression with intravascular volume repletion could lead to unintended overcorrection.

The SALSA trial found that when administering hypertonic saline to patients with symptomatic severe hyponatremia, both slow continuous infusion and rapid intermittent bolus therapy are effective and safe, with no difference in the overcorrection risk. However, bolus therapy showed better efficacy in achieving the target correction rate within 1 hour (32.2% vs 17.6% of patients receiving continuous infusion). In addition, fewer patients receiving bolus therapy required treatment to relower their serum sodium levels (41.4% vs 57.1%, respectively). The SALSA trial, conducted in Korea, was a prospective, multicenter, open-label, randomized clinical trial that enrolled 178 adult patients with moderately severe to severe hyponatremia and glucose-corrected serum sodium levels of 125 mmol/L or less. [38]

In a single-institution German study of 62 consecutive patients with symptomatic hyponatremia that compared bolus treatment (150 mL of 3% hypertonic saline) with conventional treatment (normal saline or discontinuation of hyponatremia-inducing medication), an increase in serum sodium by at least 5 mEq/L over 24 hours occurred more often with bolus treatment (62% vs 22%, respectively). However, bolus treatment resulted in a high rate of overcorrection, especially in severely symptomatic patients. These authors suggest that reducing bolus volume and reevaluating the patient before giving a repeat bolus infusion might prevent overcorrection. [39]

Pharmacologic treatment

Pharmacologic agents can be used in some cases of more refractory SIADH, allowing more liberal fluid intake. Demeclocycline has been the drug of choice to increase the diluting capacity of the kidneys, by achieving vasopressin antagonism and a functional diabetes insipidus. This treatment requires 3-4 days for maximal effect. Demeclocycline is contraindicated in cirrhotic patients. Other agents, such as lithium, have been used with variable success. Lithium can have several untoward effects, including thyroid dysfunction, interstitial kidney disease, and, in overdosage, CNS dysfunction, which make its use problematic. The treatment of psychogenic polydipsia can be difficult and may require psychiatric, pharmacologic, and fluid intervention.


Arginine vasopressin (AVP) receptor antagonists (vaptans) are a relatively new class of drugs designed specifically to promote aquaresis (ie, electrolyte-sparing excretion of free water). [40, 41] The first agent in this class to be approved was conivaptan, a V1A and V2 vasopressin receptor antagonist. It is available only for intravenous use and is approved for use in the hospital setting for euvolemic and hypervolemic hyponatremia. It is contraindicated in hypovolemic patients. It induces both a water and sodium diuresis with improvement in plasma sodium levels. Most of the clinical experience has been in heart failure. It is effective in raising serum sodium levels; however, conivaptan has not been shown to improve heart failure per se. Close monitoring of the rate of correction is needed. Conivaptan is approved for treatment for only 4 days.

In addition, the effects in patients with kidney and liver impairment have not been well studied and caution is advised with use in this population. There are several drug interactions that need close monitoring and the use of conivaptan with CYP3A4 inhibitors is contraindicated.

Tolvaptan, a selective V2 receptor antagonist, can be taken orally and has been approved for use in the treatment of euvolemic and hypervolemic hyponatremia, including cases associated with cirrhosis and heart failure. Tolvaptan treatment must be initiated in the hospital to avoid the possibility of too rapid correction (although there have not been reported cases). It also interacts with CYP3A inhibitors and use with such drugs is contraindicated. In 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. [42]

The use of these vaptans is limited and exact benefits have yet to be determined. There are reports that even mild hyponatremia can cause gait instability and possibly increase the risk of falls and hip fractures. In this setting, vaptans may be beneficial to improve hyponatremia and gait.



Free water restriction often is appropriate for patients with normovolemic hypotonic hyponatremia.

Individuals who are undernourished need to maintain an appropriate solute intake. In fact, in patients with SIADH, a high protein intake increases the solute load for excretion, thereby removing more free water. Although unpalatable, oral urea has been used to achieve the same effect.

Patients with hyperglycemia or hyperlipidemia should receive appropriate nutritional counseling.