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

From the Guidelines

Hyponatremia should be treated based on its severity, onset speed, and underlying cause, with the goal of correcting serum sodium levels without exceeding 8 mEq/L per 24-hour period to prevent osmotic demyelination syndrome, as recommended by the most recent guidelines 1.

Treatment Approach

The treatment of hyponatremia depends on its classification into hypovolemic, euvolemic, or hypervolemic types.

• For hypovolemic hyponatremia, fluid resuscitation with saline solution is necessary, along with the correction of the underlying cause of dehydration 1.
• In cases of hypervolemic hyponatremia, discontinuation of intravenous fluid therapy and free water restriction should be considered, especially if the serum sodium concentration is below 120-125 mmol/L and neurologic symptoms are present 1.

Correction Rate

The correction rate of serum sodium should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome, with a goal rate of increase of 4-6 mEq/L per 24-hour period for chronic hyponatremia in patients with cirrhosis 1.

Medications and Interventions

Medications like tolvaptan may be used for euvolemic or hypervolemic hyponatremia, and vasopressin receptor antagonists can raise serum sodium during treatment but should be used with caution and for a short term (≤30 days) 1.

• Hypertonic saline administration is reserved for short-term treatment of patients with symptomatic or severe hyponatremia or those with imminent liver transplant (LT) 1.

Monitoring and Management

Regular monitoring of serum sodium, fluid status, and neurological signs is essential during treatment, and multidisciplinary coordinated care may mitigate the risk of osmotic demyelination syndrome in patients with severe hyponatremia undergoing liver transplant 1. Some key points to consider in the management of hyponatremia include:

• Addressing the underlying cause of hyponatremia, such as discontinuing offending medications or managing heart failure or cirrhosis.
• Using albumin infusion in cases of severe hyponatremia, as it may improve serum sodium concentration.
• Being cautious with the use of hypertonic saline, as it can worsen edema and ascites in patients with cirrhosis 1.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH) 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, as evidenced by the significant increase in serum sodium levels compared to placebo in clinical studies 2, 2, and 2.

• The studies showed that tolvaptan caused a statistically greater increase in serum sodium during both periods in both studies.
• Tolvaptan is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia.
• 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.

From the Research

Definition and Prevalence of Hyponatremia

• Hyponatremia is defined by 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
• Hyponatremia can result from water retention and is associated with increased hospital stay and mortality, even in mild cases 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 3
• Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3

Diagnosis and Management of Hyponatremia

• Clinicians should categorize patients according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3, 4
• Treatment should be based on the underlying cause of hyponatremia and the patient's volume status 3, 4, 5
• 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 should be treated with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 4, 6

Treatment Options for Hyponatremia

• Hypovolemic hyponatremia is treated with normal saline infusions 4, 5
• Euvolemic hyponatremia is treated with restricting free water consumption or using salt tablets or intravenous vaptans 4, 5
• Hypervolemic hyponatremia is treated primarily by managing the underlying cause and free water restriction 4, 5
• Vaptans can be effective in managing the syndrome of inappropriate antidiuresis and hyponatremia in patients with heart failure 3, 7
• Desmopressin can be used to prevent overcorrection of hyponatremia in certain cases 6