From the Guidelines
Hyponatremia should be treated based on its severity, symptoms, and underlying cause, with the goal of correcting serum sodium levels while minimizing the risk of osmotic demyelination syndrome and other complications, as recommended by the most recent guidelines 1.
Treatment Approach
The treatment of hyponatremia depends on several factors, including the severity of the condition, the presence of symptoms, and the underlying cause.
- For mild asymptomatic hyponatremia, fluid restriction to 800-1000 mL/day may be sufficient.
- In cases of moderate to severe symptomatic hyponatremia, especially with neurological symptoms, 3% hypertonic saline may be administered intravenously at 100-150 mL over 10-20 minutes, which can be repeated if symptoms persist.
- The correction rate should not exceed 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as emphasized in recent guidelines 1.
Underlying Cause Management
It is crucial to address the underlying causes of hyponatremia, such as:
- Adjusting medications
- Treating infections
- Managing heart failure or liver disease Regular monitoring of serum sodium levels is essential during correction to avoid overcorrection and mitigate the risk of complications.
Specific Considerations
- For hypovolemic hyponatremia, treatment involves discontinuation of diuretics and/or laxatives and providing fluid resuscitation, typically with 5% IV albumin or crystalloid solution 1.
- For euvolemic hyponatremia, management should be based on the specific underlying cause.
- In cases of hypervolemic hyponatremia, treatment includes fluid restriction, reduction or discontinuation of diuretics and laxatives, administration of hyperoncotic albumin, and/or vasopressin receptor antagonists (“vaptans”) 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's Effect on Hyponatremia: Tolvaptan has been shown to cause a statistically significant increase in serum sodium levels in patients with euvolemic or hypervolemic hyponatremia.
- The studies demonstrated that tolvaptan increased serum sodium concentrations, with a mean increase of 4.0 mEq/L at Day 4 and 6.2 mEq/L at Day 30, compared to 0.4 mEq/L and 1.8 mEq/L with placebo, respectively.
- This effect was consistent across different disease etiology subsets, including heart failure, liver cirrhosis, and SIADH.
- The percentage of patients needing fluid restriction was also significantly lower in the tolvaptan group compared to the placebo group 2.
From the Research
Definition and Prevalence of Hyponatremia
- Hyponatremia is defined as a serum sodium concentration <135mmol/l 3
- It is the most common electrolyte disorder, affecting approximately 5% of adults and 35% of hospitalized patients 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 3
Causes and Classification of Hyponatremia
- Hyponatremia is usually caused by dysregulation of arginine vasopressin (AVP) homeostasis, which accompanies disorders associated with water retention such as congestive heart failure and cirrhosis, or follows euvolemic states such as syndrome of inappropriate secretion of antidiuretic hormone 5
- Hyponatremia can be classified into three categories based on fluid volume status: hypovolemic, euvolemic, and hypervolemic hyponatremia 4
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) 4
- Symptom severity depends on the rapidity of development, duration, and severity of hyponatremia 4
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 4
Treatment of Hyponatremia
- 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
- Vasopressin receptor antagonists, such as conivaptan, lixivaptan, and tolvaptan, are effective for the treatment of euvolemic and hypervolemic hyponatremia 5, 6, 7
- Hypertonic saline is reserved for patients with severely symptomatic hyponatremia, and should be used to increase the serum sodium level by 4-6 mEq/L within 1-2 hours, but by no more than 10 mEq/L within the first 24 hours 4