What is hyponatremia?

Hyponatremia is a condition in which there is an excess of body water relative to body sodium1

Often defined as serum sodium concentration < 135 mEq/L

[Na+] < 135 mEq/L

Hyponatremia may be depletional, or dilutional2,3

  • Depletional hyponatremia results from body electrolyte losses that are in excess of body water losses.3
  • Dilutional hyponatremia results from retained water and is often associated with an excessive secretion of vasopressin.2,3

Hypotonic hyponatremia is classified into 3 main categories

These categories are based on the initial assessment of the patient's volume status, medical history, urine osmolality, and sodium concentration.1,3

The 3 main categories with their volume status are illustrated below.

Hyponatremia Category Total Body Water Total Body Sodium Extracellular Fluid Edema
Hypovolemic Reduced Reduced Reduced Absent

Definition: A depletional form of hyponatremia that occurs when there is loss of sodium that exceeds water loss.1,3

SAMSCA is contraindaicated in hypovolemic and depletional hyponatremia, therefore this review focuses on euvolemic and hypervolemic hyponatremia.

Euvolemic Increased Unchanged Increased Absent

Definition: A dilutional form of hyponatremia that occurs when the total serum sodium is normal or near normal, but the total body water is increased without clinically evident edema.1,3

  • Euvolemic hyponatremia is the form of hyponatremia most commonly found in hospitalized patients4

Common Etiologies:
Syndrome of inappropriate antidiuretic hormone (SIADH). SIADH is the most common cause of euvolemic hyponatremia.1,4

Other Etiologies:
Glucorticoid deficiency

Clinical Signs: No signs of volume depletion or volume expansion.1,3

Hypervolemic Increased Increased Greatly Increased Present

Definition: A dilutional form of hyponatremia that occurs when there is an increase in total body water but a relatively smaller increase in the total serum sodium, so the available sodium is effectively diluted.1,3

Common Etiologies: Heart failure and renal disease (nephrotic syndrome and acute and chronic renal failure) are 2 primary causes of hypervolemic hyponatremia.1

Clinical signs: Signs of volume expansion, such as the presence of clinically evident edema, ascites, and pulmonary edema.3

The figure below provides a guide for classifying hyponatremia into categories.

Algorithm for classifying hyponatremia
A guide for classifying hyponatremia into the 3 categories

Based on assessment of volume status, medical history, and urine osmolality and sodium concentrations, hyponatremia can be classified as hypovolemic, euvolemic, or hypervolemic. Douglas I. Hyponatremia: why it matters, how it presents, how we can manage it. Cleve Clin J Med. 2006;73(suppl 3):S4-S12. Reprinted with permission. Copyright © 2006 Cleveland Clinic. All rights reserved.

Prevalence of Hyponatremia:

In the United States, the estimated prevalence of hyponatremia ranges from 3.16 million to 6.07 million persons.5

Risk Factors

Certain medical conditions and medications have the potential to increase the risk of hyponatremia.2,6

Risk Factors for Hyponatremia 2,6
Selected Conditions3 Selected Drug Classes6
  • Surgery or injury
  • Very young or very old age
  • Renal dysfunction
  • Adrenal insufficiency
  • Hypothryoidism
  • Congestive heart failure
  • Central nervous system impairment
  • Diuretics
  • Antipsychotics
  • Tricyclic antidepressants
  • Selective reotonin reuptake inhibitors
  • Opiate derivatives
  • Antiepileptic agents(carbamazepine and lamotrigine)
  • Anticancer agents
  • Nonsteroidal anti-inflammatory drugs

Signs & Symptoms

Patients who experience hyponatremia may exhibit clinical manifestations that are largely related to central nervous system dysfunction. Signs and symptoms are important to recognize.2,7

Signs and Symptoms of Hyponatremia7 Complications of Severe Hyponatremia2,7
  • Headache
  • Nausea
  • Vomiting
  • Muscle cramps
  • Lethargy
  • Restlessness
  • Disorientation
  • Depressed reflexes
  • Seizures
  • Hallucinations
  • Acute psychosis
  • Coma

It has not been established that raising serum sodium with SAMSCA® (tolvaptan) provides a symptomatic benefit to patients