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

From the Guidelines

Hyponatremia management should prioritize a tailored approach based on severity, symptoms, and underlying cause, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome, 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 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) requires a more severe restriction of water intake with albumin infusion 1.
• Vasopressin receptor antagonists can be used with caution for a short term (≤30 days) to raise serum sodium in cirrhosis, but their use should be carefully considered due to potential risks 1.

Treatment Approaches

• Hypertonic saline (3%) administration is reserved for short-term treatment of patients with symptomatic or severe hyponatremia, or those with imminent liver transplant, with a goal of raising serum sodium by 4-6 mEq/L in the first 24 hours 1.
• The goal rate of increase of serum sodium is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period to ameliorate the risk of osmotic demyelination syndrome 1.
• Fluid restriction to 1–1.5 L/day should be reserved for those who are clinically hypervolaemic with severe hyponatraemia (serum sodium <125 mmol/day) 1.

Monitoring and Prevention

• Monitor serum sodium every 4-6 hours during active correction, aiming for a maximum increase of 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1.
• Potassium replacement should be considered alongside sodium correction as potassium also contributes to tonicity, and nutritional support with adequate protein intake helps maintain plasma oncotic pressure and prevents further sodium dilution.

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 Overview

• Hyponatremia is defined as a serum sodium level of less than 135 mEq/L and is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3.
• The management of hyponatremia should be based on the underlying cause and the patient's fluid volume status, which can be categorized as hypovolemic, euvolemic, or hypervolemic hyponatremia 3, 4.

Treatment Approaches

• For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 3, 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 3, 5.
• Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency and should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 4, 6.

Considerations for Treatment

• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition, which can result in parkinsonism, quadriparesis, or even death 3, 4, 6.
• The correction limit for serum sodium level should not exceed 10 mEq/L within the first 24 hours to avoid osmotic demyelination 3, 4.
• Vasopressin receptor antagonists (VRA) can be used to treat euvolemic and hypervolemic hyponatremia, and have been shown to be effective in increasing serum sodium concentration 5.

Clinical Practice Guidelines

• The European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE), and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia 7.
• These guidelines provide a holistic view of the management of hyponatremia and focus on patient-positive outcomes and providing a useful tool for clinicians involved in everyday practice 7.