What is the evaluation and treatment of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia treatment should prioritize correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome, with the goal of improving morbidity, mortality, and quality of life.

Evaluation and Treatment Approach

Hyponatremia evaluation begins with assessing volume status (hypovolemic, euvolemic, or hypervolemic) and measuring serum and urine osmolality and sodium. Treatment depends on severity, chronicity, and underlying cause.

• For severe symptomatic hyponatremia (serum sodium <120 mEq/L with seizures or altered mental status), administer 3% hypertonic saline at 100-150 mL over 10-20 minutes, which can be repeated, aiming for a sodium correction rate of 4-6 mEq/L in the first 6 hours and not exceeding 8-10 mEq/L in 24 hours to avoid osmotic demyelination syndrome, as recommended by 1.
• For chronic hyponatremia, correct more slowly at 4-6 mEq/L per day.

Specific Treatments

Specific treatments include:

• Fluid restriction for SIADH (500-1000 mL/day)
• Salt tablets and fludrocortisone for cerebral salt wasting
• Loop diuretics like furosemide 20-40 mg IV for hypervolemic states
• Isotonic saline for hypovolemic hyponatremia
• Tolvaptan, a vasopressin receptor antagonist, may be used for euvolemic or hypervolemic hyponatremia starting at 15 mg daily with close monitoring, as discussed in 1.

Monitoring and Prevention of Complications

Discontinue offending medications if present. Frequent sodium monitoring (every 2-4 hours initially for severe cases) is essential to ensure appropriate correction rates and prevent complications, such as osmotic demyelination syndrome, as highlighted in 1.

Underlying Pathophysiology

The underlying pathophysiology involves water and sodium imbalance, with excess water retention relative to sodium being the primary mechanism in most cases. The most recent and highest quality study, 1, provides guidance on the management of hyponatremia, emphasizing the importance of careful correction of serum sodium levels to minimize the risk of complications.

From the FDA Drug Label

14 CLINICAL STUDIES 14. 1 Hyponatremia 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.

Fluid restriction was to be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium, and during the first 24 hours of therapy 87% of patients had no fluid restriction. The dose of tolvaptan could be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) was reached

The evaluation and treatment of hyponatremia with tolvaptan involves:

• Avoiding fluid restriction during the first 24 hours of therapy to prevent overly rapid correction of serum sodium
• Initiating tolvaptan at an oral dose of 15 mg once daily, with possible increases to 30 mg and 60 mg once daily
• Monitoring serum sodium concentrations regularly, including at 8 hours after study drug initiation and daily up to 72 hours
• Maintaining treatment for 30 days, with additional serum sodium assessments on Days 11,18,25, and 30
• Considering the use of tolvaptan in patients with euvolemic or hypervolemic hyponatremia, including those with heart failure, liver cirrhosis, and SIADH 2 Key points:
• Tolvaptan causes a statistically greater increase in serum sodium compared to placebo
• The effect of tolvaptan is seen across all disease etiology subsets, including CHF, cirrhosis, and SIADH/other
• Tolvaptan reduces the need for fluid restriction in patients with hyponatremia 2

From the Research

Evaluation of Hyponatremia

• Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 3.
• Symptoms and signs of hyponatremia range from mild and nonspecific (such as weakness or nausea) to severe and life-threatening (such as seizures or coma) 3.
• When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3, 4.

Treatment of Hyponatremia

• For most patients, the approach to managing hyponatremia should consist of treating the underlying cause 3.
• 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.
• 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, 5, 6.
• The European guidelines recommend treating severely symptomatic hyponatremia with bolus-wise administration of 150 mL of 3% hypertonic saline 6.
• Overly rapid correction of chronic hyponatremia may cause osmotic demyelination, a rare but severe neurological condition 3, 5.

Management of Specific Types of Hyponatremia

• Hypovolemic hyponatremia is managed by rehydration with isotonic saline 4.
• Hypervolemic hyponatremia is managed by addressing the underlying cause 4.
• Euvolemic hyponatremia is managed by restricting free water intake, addressing the underlying cause, and occasionally with drugs (eg, vasopressin receptor antagonists) 4, 7.
• Vasopressin receptor antagonists are potential tools in the management of hyponatremia, particularly in the treatment of euvolemic and hypervolemic hyponatremia 7.