What are the stratifications of hyponatremia (low sodium levels)?

From the Guidelines

Hyponatremia should be stratified based on serum sodium levels, onset timing, and symptom severity, with treatment approaches varying by stratification to prioritize morbidity, mortality, and quality of life outcomes. The stratification of hyponatremia is crucial in determining the urgency and treatment approach. According to the most recent and highest quality study 1, hyponatremia can be classified as mild (130-135 mEq/L), moderate (125-129 mEq/L), and severe (below 125 mEq/L). The onset of hyponatremia can be acute (within 48 hours) or chronic (over 48 hours), and symptoms can range from asymptomatic to severe neurological symptoms like headache, confusion, seizures, or coma.

Stratification and Treatment Approach

The treatment approach varies by stratification:

• Mild asymptomatic cases often need only fluid restriction and addressing underlying causes
• Moderate cases may require careful sodium correction with isotonic or hypertonic saline
• Severe or symptomatic cases require immediate intervention with 3% hypertonic saline, typically 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 highlighted in the study 1. Volume status assessment (hypovolemic, euvolemic, or hypervolemic) is crucial for determining the underlying cause and guiding appropriate treatment.

Key Considerations

• Fluid restriction to 1–1.5 L/day should be reserved for those who are clinically hypervolaemic with severe hyponatraemia (serum sodium <125 mmol/L), as recommended in the study 1
• Hypertonic sodium chloride (3%) administration should be reserved for those who are severely symptomatic with acute hyponatraemia, with slow correction of serum sodium levels, as suggested in the study 1
• The use of midodrine in refractory ascites may be considered on a case-by-case basis, as mentioned in the study 1

Prioritizing Outcomes

In prioritizing morbidity, mortality, and quality of life outcomes, it is essential to consider the most recent and highest quality evidence, such as the study 1, which provides guidelines on the management of ascites in cirrhosis. By stratifying hyponatremia and tailoring treatment approaches, clinicians can determine urgency, treatment approach, and correction rates based on the physiological impact of sodium imbalance on cellular function and brain adaptation.

From the FDA Drug Label

For patients with a serum sodium of <130 mEq/L or <125 mEq/L, the effects at Day 4 and Day 30 remained significant Subgroup with Serum Sodium <130 mEq/L Change in average daily serum [Na+] AUC baseline to Day 4 (mEq/L) Mean (SD) N 4.8 (3.0) 110 0.7 (2.5) 105 4.2 (3.5 to 5.0) p <0. 0001 Change in average daily serum [Na+] AUC baseline to Day 30 (mEq/L) Mean (SD) N 7.9 (4.1) 110 2.6 (4.2) 105 5.5 (4.4 to 6.5) p <0.0001 Subgroup with Serum Sodium <125 mEq/L Change in average daily serum [Na+] AUC baseline to Day 4 (mEq/L) Mean (SD) N 5.7 (3.8) 26 1.0 (1.8) 30 5.3 (3.8 to 6.9) p <0. 0001 Change in average daily serum [Na+] AUC baseline to Day 30 (mEq/L) Mean (SD) N 10.0 (4.8) 26 4.1 (4.5) 30 5.7 (3.1 to 8.3) p <0.0001

The stratification of hyponatremia can be based on the following serum sodium levels:

• Mild hyponatremia: 130-134 mEq/L
• Moderate hyponatremia: 125-129 mEq/L
• Severe hyponatremia: <125 mEq/L Tolvaptan is effective in correcting serum sodium levels in patients with euvolemic or hypervolemic hyponatremia, including those with severe hyponatremia 2.

From the Research

Stratification of Hyponatremia

Hyponatremia can be stratified based on the patient's fluid volume status, which is crucial for determining the underlying cause and guiding treatment. The main categories are:

• Hypovolemic hyponatremia: characterized by decreased extracellular fluid volume 3, 4, 5
• Euvolemic hyponatremia: characterized by normal extracellular fluid volume 3, 4, 5
• Hypervolemic hyponatremia: characterized by increased extracellular fluid volume 3, 4, 5

Causes and Symptoms

The causes of hyponatremia are multifactorial and can be due to various conditions such as heart failure, syndrome of inappropriate antidiuresis (SIADH), and cerebral salt wasting syndrome 3, 4, 6. Symptoms of hyponatremia can range from mild and nonspecific to severe and life-threatening, depending on the rapidity of development, duration, and severity of the condition 3, 4.

Treatment Approaches

Treatment of hyponatremia depends on the underlying cause, severity, and symptoms. The main treatment approaches include:

• Treating the underlying cause 3, 5
• Fluid restriction and/or diuretics for hypervolemic hyponatremia 4, 5
• Normal saline for hypovolemic hyponatremia 5
• 3% NaCl and fluid restriction for euvolemic hyponatremia 5
• Vasopressin receptor antagonists (vaptans) for euvolemic and hypervolemic hyponatremia 6, 7

Special Considerations

Severely symptomatic hyponatremia is a medical emergency and requires prompt treatment with bolus hypertonic saline to reverse hyponatremic encephalopathy 3, 4. Overly rapid correction of chronic hyponatremia can cause osmotic demyelination, a rare but severe neurological condition 3, 4.