From the Guidelines
Evaluation of hyponatremia should begin with confirming the low sodium level and assessing the patient's volume status, with treatment guided by the most recent and highest quality study, which recommends the use of vasopressin receptor antagonists like tolvaptan for euvolemic and hypervolemic hyponatremia 1. The first step in evaluating hyponatremia is to determine the patient's volume status, which can be hypovolemic, euvolemic, or hypervolemic. Essential laboratory tests include serum osmolality, urine sodium, urine osmolality, thyroid function tests, morning cortisol, and kidney function tests.
- For hypovolemic hyponatremia, fluid resuscitation with isotonic saline is appropriate.
- In euvolemic hyponatremia, fluid restriction to 800-1000 mL/day is often recommended, while SIADH may require vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) 1.
- Hypervolemic hyponatremia typically requires sodium and fluid restriction along with diuretics like furosemide (20-40 mg daily). Correction rates should not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as recommended by the most recent guidelines 1. Severe symptomatic hyponatremia (sodium <120 mEq/L with neurological symptoms) may require 3% hypertonic saline at 1-2 mL/kg/hr with frequent monitoring. The underlying cause of hyponatremia must be addressed, whether it's medication-induced, hormonal deficiencies, or other medical conditions. Regular monitoring of serum sodium levels during correction is essential to ensure appropriate treatment and prevent complications, with the goal of improving morbidity, mortality, and quality of life 1. It is also important to note that the use of vaptans, such as tolvaptan, has been shown to be effective in improving serum sodium concentration in patients with hypervolemic hyponatremia, but requires close monitoring to avoid complications such as hypernatremia, dehydration, and renal impairment 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.
The evaluation of hyponatremia involves assessing 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.
- Key findings:
- Tolvaptan caused a statistically greater increase in serum sodium compared to placebo.
- The effect was seen across all disease etiology subsets (e.g., CHF, cirrhosis, SIADH/other).
- The percentage of patients requiring fluid restriction was significantly less in the tolvaptan-treated group compared to the placebo-treated group. 2
From the Research
Evaluation of Hyponatremia
The evaluation of hyponatremia, a condition characterized by low sodium levels, involves a comprehensive approach to determine the underlying cause and severity of symptoms. Key aspects of evaluation include:
- Detailed history and physical examination to assess volume status and identify potential causes 3
- Laboratory studies, such as urine and serum osmolality, urine sodium concentration, and serum electrolyte levels, to classify the type of hyponatremia and guide treatment decisions 3, 4, 5
- Estimation of volume status, which can be hypovolemic, euvolemic, or hypervolemic, to inform treatment strategies 4, 6
- Point-of-care ultrasonography as an adjunct to physical assessment in estimating volume status 6
Classification and Diagnosis
Hyponatremia can be classified based on volume status and plasma osmolality. The main categories include:
- Hypovolemic hyponatremia, characterized by low blood volume and low sodium levels
- Euvolemic hyponatremia, with normal blood volume and low sodium levels
- Hypervolemic hyponatremia, with high blood volume and low sodium levels
- Diagnosis is based on findings from history, physical examination, laboratory studies, and evaluation of volume status 4, 7, 5
Clinical Manifestations and Treatment
The clinical manifestations of hyponatremia can range from mild to severe and include headache, dizziness, nausea/vomiting, seizures, obtundation, and death 3, 5. Treatment decisions are based on the underlying cause and severity of symptoms, and may involve: