From the Guidelines
Hyponatremia should be treated with caution, prioritizing the correction rate to avoid osmotic demyelination syndrome, with a goal of raising sodium by 4-6 mEq/L in the first 24 hours, not to exceed 8 mEq/L per 24-hour period, as recommended by the most recent guidelines 1.
Treatment Approach
The treatment of hyponatremia depends on the severity, symptoms, and underlying cause. For mild asymptomatic hyponatremia, fluid restriction to 800-1000 mL/day is often sufficient.
- For moderate to severe symptomatic hyponatremia, 3% hypertonic saline may be administered intravenously at 1-2 mL/kg/hour.
- Specific medications may include vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) for SIADH, or loop diuretics like furosemide (20-40 mg IV) for fluid overload states.
Correction Rate
The correction rate of sodium is crucial to prevent osmotic demyelination syndrome.
- The goal is to raise sodium by 4-6 mEq/L in the first 24 hours, not to exceed 8 mEq/L per 24-hour period, as recommended by the American Association for the Study of Liver Diseases 1.
- Frequent monitoring of serum sodium levels is necessary to avoid overcorrection, which can lead to central pontine myelinolysis or seizures, as highlighted in the guidelines for the management of ascites in cirrhosis 1.
Underlying Cause
The underlying cause of hyponatremia must be addressed simultaneously, whether it's medication-induced, due to heart failure, liver disease, or endocrine disorders.
- For hypovolemic hyponatremia, fluid resuscitation is needed, while for hypervolemic hyponatremia, discontinuation of intravenous fluid therapy and free water restriction should be considered, as recommended by the Korean Association for the Study of Liver Diseases 1.
Monitoring
Sodium correction should be carefully monitored with serum sodium checks every 2-4 hours in severe cases.
- Hyponatremia requires careful management because the brain adapts to low sodium levels; correcting too quickly can lead to permanent neurological damage, while correcting too slowly risks continued cerebral edema and neurological symptoms, including seizures, coma, and potentially death, as emphasized in the guidelines for the management of heart failure 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 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
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
- Mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 3
- Severely symptomatic hyponatremia (with signs of somnolence, obtundation, coma, seizures, or cardiorespiratory distress) is a medical emergency 3
Diagnosis and Management of Hyponatremia
- When evaluating patients, clinicians should categorize them according to their fluid volume status (hypovolemic hyponatremia, euvolemic hyponatremia, or hypervolemic hyponatremia) 3
- 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, 5, 6
- Hypertonic saline is reserved for patients with severely symptomatic hyponatremia 3
Treatment Options
- Vasopressin-2 receptor antagonists (vaptans) provide a new approach to the treatment of hyponatremia 5, 6
- Vaptans lead to aquaresis, an electrolyte-sparing excretion of free water, that results in the correction of serum sodium concentration 6
- Conivaptan has been approved by the FDA for the treatment of euvolemic hyponatremia 6
- European guidelines recommend treating severely symptomatic hyponatremia with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 4