What is the management of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia management should prioritize a careful approach based on severity, symptoms, and underlying cause, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome and other complications, as recommended by the most recent guidelines 1.

Key Considerations

• For mild hyponatremia (Na 126-135 mEq/L) in cirrhosis without symptoms, no specific management is required apart from monitoring and water restriction, as stated in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1.
• For moderate hyponatremia (120-125 mEq/L), water restriction to 1,000 mL/day and cessation of diuretics is recommended, while severe hyponatremia (<120 mEq/L) may require a more severe restriction of water intake with albumin infusion, as suggested by the same guidelines 1.
• The use of vasopressin receptor antagonists can raise serum sodium during treatment, but they should be used with caution only for a short term (≤30 days) 1.
• Hypertonic saline is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant, with a goal of correcting serum sodium by 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period, as recommended by the guidelines 1.

Treatment Approaches

• Fluid restriction to 800-1000 mL/day is the mainstay of treatment for chronic or asymptomatic hyponatremia, particularly in SIADH.
• Medications like tolvaptan or urea may be used in euvolemic hyponatremia.
• For hypovolemic hyponatremia, isotonic saline (0.9% NaCl) should be administered to restore volume.
• In hypervolemic states, loop diuretics like furosemide combined with fluid restriction are effective.

Monitoring and Correction

• Monitor serum sodium every 4-6 hours initially, aiming for correction rates not exceeding 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome.
• Addressing the underlying cause, whether it's medications, endocrine disorders, or other conditions, is essential for definitive management.
• Rapid correction risks permanent neurological damage, while insufficient treatment may leave patients at risk for seizures and other complications, as highlighted by the guidelines 1.

From the FDA Drug Label

In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal. The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Compared to placebo, tolvaptan caused a statistically greater increase in serum sodium ( p <0. 0001) during both periods in both studies.

Hyponatremia Management with Tolvaptan: Tolvaptan is effective in managing hyponatremia, with a statistically significant increase in serum sodium levels compared to placebo.

• The treatment effect was seen across all disease etiology subsets, including heart failure, liver cirrhosis, and SIADH.
• Tolvaptan can be initiated at a dose of 15 mg once daily, with possible titration to 30 mg and 60 mg once daily, as needed, to achieve normonatremia.
• Fluid restriction should be avoided during the first 24 hours of therapy to prevent overly rapid correction of serum sodium 2.

From the Research

Hyponatremia Management

• Hyponatremia is considered mild when the sodium concentration is 130 to 134 mEq per L, moderate when 125 to 129 mEq per L, and severe when less than 125 mEq per L 3
• Patients with a sodium concentration of less than 125 mEq per L and severe symptoms require emergency infusions with 3% hypertonic saline 3
• Management to correct sodium concentration is based on whether the patient is hypovolemic, euvolemic, or hypervolemic 3
• Hypovolemic hyponatremia is treated with normal saline infusions, while euvolemic hyponatremia includes restricting free water consumption or using salt tablets or intravenous vaptans 3
• Hypervolemic hyponatremia is treated primarily by managing the underlying cause and free water restriction 3

Treatment Approaches

• For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 4
• Urea and vaptans can be effective treatments for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure, but have adverse effects 4
• Severely symptomatic hyponatremia is a medical emergency and should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 4
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition 4, 5, 6

Monitoring and Risks

• Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia 7
• Rapid correction of severe hyponatremia carries the risk of osmotic demyelination 7
• Prevention of osmotic demyelination syndrome should be a prime concern of the treatment of hypotonic hyponatremia 5