From the Guidelines
Hyponatremia should be treated based on its severity and symptoms, with the goal of correcting sodium levels without exceeding 8 mmol/L per 24-hour period to prevent osmotic demyelination syndrome, as recommended by the most recent guidelines 1.
Treatment Approaches
- For mild to moderate cases (sodium 125-135 mEq/L), fluid restriction to 800-1000 mL/day is often the first approach.
- For symptomatic or severe hyponatremia (sodium <125 mEq/L), 3% hypertonic saline may be administered intravenously at 1-2 mL/kg/hour, with careful monitoring to avoid correcting sodium levels too quickly.
- The use of vasopressin receptor antagonists, such as tolvaptan, may be considered for short-term treatment of patients with symptomatic or severe hyponatremia, especially in cases of SIADH-related hyponatremia.
Key Considerations
- Addressing the underlying cause of hyponatremia is crucial, whether it's medication-induced, heart failure, liver disease, or adrenal insufficiency.
- Patients should be monitored with regular electrolyte checks during correction to prevent overcorrection and osmotic demyelination syndrome.
- The correction rate should not exceed 8-10 mmol/L in the first 24 hours and 18 mmol/L in 48 hours to prevent osmotic demyelination syndrome, as supported by recent guidelines 1.
Special Considerations
- In patients with liver cirrhosis, hyponatremia should be treated with caution, as excessive correction of sodium levels can worsen ascites and edema, as noted in studies 1.
- In cases of heart failure, vasopressin antagonists may be used to improve serum sodium concentration, but their long-term safety and benefit remain unknown, as discussed in 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
- 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 is indicated for the treatment of euvolemic or hypervolemic hyponatremia.
- The primary endpoint of the 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 2.
From the Research
Definition and Prevalence of Hyponatremia
- Hyponatremia is defined as a serum sodium level of less than 135 mEq/L 3
- It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 3, 4
- Hyponatremia can lead to a wide spectrum of clinical symptoms, from mild to severe or even life-threatening, and is associated with increased mortality, morbidity, and length of hospital stay 4
Causes and Classification of Hyponatremia
- Hyponatremia most commonly results from water retention 3
- It can be classified into three categories based on fluid volume status: hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia 3
- Etiologies of hyponatremia include excessive intake of solute-free fluids, side-effects of medication, diseases associated with hypervolemic states such as congestive heart failure, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 5
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 3
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3
Treatment and Management 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
- Vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity 6, 7