What is the cause of persistent hyponatremia (low sodium levels) with euvolemia (normal fluid volume) and hypo-osmolar (low osmolarity) state?

From the Guidelines

Persistent euvolemic hypo-osmolar hyponatremia should be managed with fluid restriction to 800-1000 mL/day as first-line therapy, and if ineffective, pharmacologic options such as vasopressin receptor antagonists like tolvaptan starting at 15 mg daily and titrating up to 60 mg if needed, should be considered. The management of euvolemic hypo-osmolar hyponatremia involves identifying and addressing the underlying cause, which is often the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.

Key Considerations

• Fluid restriction is the first-line therapy, aiming to restrict fluid intake to 800-1000 mL/day.
• If fluid restriction is ineffective, pharmacologic options such as oral urea, salt tablets, or vasopressin receptor antagonists like tolvaptan may be considered.
• Loop diuretics like furosemide may be added to enhance free water excretion.
• For severe symptomatic hyponatremia, 3% hypertonic saline should be administered with a goal to increase sodium by 4-6 mEq/L in the first 24 hours to prevent osmotic demyelination syndrome.
• Regular monitoring of serum sodium, osmolality, and volume status is essential, with sodium correction not exceeding 8 mEq/L in 24 hours for chronic cases to prevent complications.

Pharmacologic Options

• Vasopressin receptor antagonists like tolvaptan, starting at 15 mg daily and titrating up to 60 mg if needed, may be effective in improving serum sodium concentration in patients with euvolemic hypo-osmolar hyponatremia 1.
• The use of vaptans, such as tolvaptan, has been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, including SIADH, heart failure, and cirrhosis 1.

Monitoring and Prevention of Complications

• Regular monitoring of serum sodium, osmolality, and volume status is essential to prevent complications such as osmotic demyelination syndrome.
• Sodium correction should not exceed 8 mEq/L in 24 hours for chronic cases to prevent complications.
• The risk of hypernatremia, dehydration, and renal impairment should be taken into account when using vaptans, and treatment should always be started in the hospital with close clinical monitoring and assessment of serum sodium levels 1.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• Tolvaptan is used to treat euvolemic hyponatremia, which is a condition where the body has a low sodium level and a normal fluid volume.
• The dosage of tolvaptan is typically started at 15 mg once daily and can be increased to a maximum of 60 mg once daily as needed to achieve the desired level of serum sodium 2.
• It is essential to monitor serum sodium concentrations and neurologic status, especially during initiation and after titration, to avoid too rapid correction of serum sodium which can cause serious neurologic sequelae 2.

From the Research

Definition and Classification of Hyponatremia

• Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 3.
• It can be classified into three categories based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, and hypervolemic hyponatremia 3, 4.

Euvolemic Hyponatremia

• Euvolemic hyponatremia is frequently encountered in hospitalized patients and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause in most patients 5.
• The diagnosis of SIADH is confirmed by decreased serum osmolality, inappropriately elevated urine osmolality (>100 mosmol/L), and elevated urine sodium (Na) levels 5.
• Clinical mimics of SIADH like cerebral salt wasting and reset osmostat should be considered in some patients 5.

Treatment of Euvolemic Hyponatremia

• Free water restriction combined with increased solute intake (e.g., urea) is the most effective therapy to treat patients with SIADH 5.
• Hypertonic (3%) saline should be used in patients with significant neurologic symptoms and maximal correction of serum Na level should be limited to <8 mEq over 24 hours to prevent osmotic demyelination syndrome (ODS) 5.
• Simultaneous administration of parenteral desmopressin is one of the best ways to prevent overly rapid Na correction in high-risk patients 5.
• Vasopressin receptor antagonists, such as tolvaptan, can be effective in treating euvolemic hyponatremia, including SIADH 6.

Complications and Associations of Hyponatremia

• Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients 6.
• Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant 6.
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3.