What are the causes and treatments of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia should be treated based on its etiology, chronicity, severity, and urgency, with the goal of correcting sodium levels gradually to avoid osmotic demyelination syndrome, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment of hyponatremia depends on whether it is acute or chronic, as well as its underlying cause. For acute hyponatremia, rapid correction may be necessary to prevent cerebral edema, but this should be done with caution to avoid overcorrection 1.

• For hypovolemic hyponatremia, discontinuation of diuretics and fluid resuscitation with 5% IV albumin or crystalloid solution is recommended 1.
• For euvolemic hyponatremia, treatment should be based on the specific underlying cause.
• For hypervolemic hyponatremia, treatment includes fluid restriction, reduction or discontinuation of diuretics and laxatives, administration of hyperoncotic albumin, and/or vasopressin receptor antagonists (“vaptans”) 1.

Correction Rate

The rate of correction is crucial to avoid complications such as osmotic demyelination syndrome.

• For chronic hyponatremia, the correction should not exceed 6-8 mmol/L in 24 hours 1.
• For acute hyponatremia, more rapid correction may be necessary, but the risk of overcorrection should be carefully managed 1.

Monitoring

Frequent electrolyte monitoring is essential during the correction of hyponatremia to avoid overcorrection or undercorrection 1.

• Monitoring should include regular checks of serum sodium levels, as well as clinical assessment for signs of overcorrection or undercorrection.

Underlying Causes

Addressing the underlying cause of hyponatremia is critical for effective management.

• This may involve discontinuing offending medications, treating underlying conditions such as heart failure or SIADH, or replacing adrenal insufficiency with hydrocortisone 1.

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.

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

• Tolvaptan is effective in treating hyponatremia by increasing serum sodium levels.
• The studies showed a statistically significant increase in serum sodium levels in patients treated with tolvaptan compared to placebo.
• Tolvaptan was effective in patients with serum sodium levels <135 mEq/L, <130 mEq/L, and <125 mEq/L.
• The effect of tolvaptan was seen across all disease etiology subsets, including heart failure, liver cirrhosis, and SIADH 2.

From the Research

Definition and Prevalence of Hyponatremia

• Hyponatremia is defined by 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.
• It most commonly results from water retention and can be categorized into hypovolemic, euvolemic, or hypervolemic hyponatremia based on fluid volume status 3.

Symptoms and Signs of Hyponatremia

• 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.
• Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia, with mild chronic hyponatremia associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3.

Treatment of Hyponatremia

• The approach to managing hyponatremia should consist of treating the underlying cause, with urea and vaptans effective for the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure 3.
• Vasopressin receptor antagonists are a promising new therapeutic option for the treatment of hyponatremia, particularly for euvolemic and hypervolemic hyponatremia 4, 5, 6.
• Hypertonic saline is reserved for patients with severely symptomatic hyponatremia, with the goal of increasing the serum sodium level by 4-6 mEq/L within 1-2 hours, but not exceeding a correction limit of 10 mEq/L within the first 24 hours 3.

Complications of Hyponatremia and Its Treatment

• Overly rapid correction of chronic hyponatremia can cause osmotic demyelination, a rare but severe neurological condition 3.
• Vasopressin receptor antagonists have been shown to be effective and safe for the treatment of hyponatremia, with an increased rate of rapid sodium correction but no significant increase in hypernatremia or adverse events 5.
• Uncertainty still exists regarding the optimal indications for the use of vasopressin receptor antagonists in hyponatremia, and there have been reports of complications resulting from their misuse 7.