From the Guidelines
Hyponatremia should be treated based on its severity and underlying cause, with the goal of correcting serum sodium levels without exceeding a rate of 8 mEq/L per 24 hours to prevent osmotic demyelination syndrome, as recommended by the American Association for the Study of Liver Diseases in 2021 1. The causes of hyponatremia can be diverse, including but not limited to, cirrhosis, heart failure, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and certain medications.
Treatment Approaches
- For mild cases (sodium >125 mEq/L) with minimal symptoms, fluid restriction to 800-1000 mL/day is often sufficient 1.
- For moderate to severe symptomatic hyponatremia, especially with neurological symptoms, 3% hypertonic saline should be administered at 100-150 mL over 10-20 minutes, which can be repeated 2-3 times if symptoms persist, as suggested by guidelines on the management of ascites in cirrhosis 2.
- The use of vasopressin receptor antagonists can raise serum sodium during treatment but should be used with caution only for a short term (≤30 days) 1.
- Regular monitoring of serum sodium levels (every 2-4 hours initially for severe cases) is essential to guide therapy.
Key Considerations
- Underlying causes must be addressed simultaneously, such as stopping offending medications, treating infections, or managing heart failure.
- The correction rate should not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, with a goal rate of increase of serum sodium of 4-6 mEq/L per 24-hour period in patients with cirrhosis 1.
- Multidisciplinary coordinated care may mitigate the risk of osmotic demyelination syndrome in patients with severe hyponatremia undergoing liver transplantation 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 causes of hyponatremia mentioned in the study include:
- Heart failure
- Liver cirrhosis
- Syndrome of inappropriate antidiuretic hormone (SIADH)
- Other underlying causes
The treatment of hyponatremia mentioned in the study is:
- Tolvaptan, a medication that can be taken orally at an initial dose of 15 mg once daily, with possible increases to 30 mg once daily and then to 60 mg once daily
- Fluid restriction, which may be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium 3
From the Research
Causes of Hyponatremia
- Hyponatremia is defined by a serum sodium level of less than 135 mEq/L and most commonly results from water retention 4
- Pathophysiologically, hyponatremias are classified into two groups: hyponatremia due to non-osmotic hypersecretion of vasopressin (hypovolemic, hypervolemic, euvolemic) and hyponatremia of non-hypervasopressinemic origin (pseudohyponatremia, water intoxication, cerebral salt wasting syndrome) 5
- The condition primarily results from the combination of impaired free water excretion due to elevated vasopressin levels in conjunction with a source of free water intake 6
Symptoms 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) 4
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 4
- Severe hyponatremia is usually associated with central nervous system symptoms and can be life-threatening 5
Treatments of Hyponatremia
- 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 (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 4, 6
- The conventional treatments for chronic asymptomatic hyponatremia (except hypovolemic patients) include water restriction and/or the use of demeclocycline or lithium or furosemide and salt supplementation 5
- Vasopressin receptor antagonists have opened a new forthcoming therapeutic era, with V2 receptor antagonists, such as lixivaptan, tolvaptan, satavaptan, promoting the electrolyte-sparing excretion of free water and leading to increased serum sodium 5