How is low serum osmolality treated?

Treatment of Low Serum Osmolality

Low serum osmolality should be treated based on the underlying cause, with fluid restriction being the first-line treatment for SIADH and appropriate fluid replacement for hypovolemic hyponatremia. 1

Diagnosis and Assessment

• Low serum osmolality is defined as a serum osmolality <275 mOsm/kg, which indicates hyposmolality 1
• Directly measured serum or plasma osmolality should be used as the primary indicator of hydration status, particularly in older adults 1, 2
• Where direct measurement is unavailable, calculated osmolarity using the equation: osmolarity = 1.86 × (Na+ + K+) + 1.15 × glucose + urea + 14 (all measured in mmol/L) can be used 1, 2
• Evaluate for symptoms which may include general weakness, confusion, headache, and nausea at serum sodium concentrations of 125-130 mEq/L 1
• Life-threatening manifestations may occur when serum sodium levels drop below 120 mEq/L 1
• Assess volume status to differentiate between euvolemic, hypovolemic, and hypervolemic hyposmolality 1

Treatment Algorithm Based on Volume Status

For Euvolemic Hyponatremia (SIADH)

• Free water restriction (<1 L/day) is the first-line treatment for asymptomatic mild SIADH 1
• For patients with moderate to severe symptomatic hyponatremia:
  • Tolvaptan (vasopressin V2-receptor antagonist) may be considered for clinically significant euvolemic hyponatremia with serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction 3
  • Starting dose is 15 mg once daily, which may be increased at intervals ≥24 hours to 30 mg once daily, and to a maximum of 60 mg once daily as needed 3
  • Tolvaptan should be initiated and re-initiated in a hospital setting where serum sodium can be monitored closely 3

For Hypovolemic Hyponatremia

• Isotonic saline (0.9% NaCl) should be administered to restore intravascular volume 1
• For mild to moderate dehydration, oral rehydration solution (ORS) should be administered 1
• For severe dehydration, isotonic intravenous fluids such as lactated Ringer's and normal saline should be administered 1

For Hypervolemic Hyponatremia

• Fluid restriction and diuretic therapy are the mainstays of treatment 1
• Salt restriction may be necessary in conditions like heart failure or cirrhosis 1

Monitoring and Rate of Correction

• Monitor serum sodium levels closely during treatment to prevent overly rapid correction 3
• Too rapid correction of hyponatremia (e.g., >12 mEq/L/24 hours) can cause osmotic demyelination resulting in serious neurological symptoms 3
• In susceptible patients, including those with severe malnutrition, alcoholism, or advanced liver disease, slower rates of correction may be advisable 3
• Hydration status should be reassessed regularly until corrected, then monitored periodically 2

Special Considerations

• For patients with life-threatening or acute symptomatic severe hyponatremia (<120 mEq/L), hypertonic 3% saline IV is indicated 1
• When using tolvaptan, monitor for potential adverse effects including thirst, dry mouth, asthenia, constipation, pollakiuria or polyuria, and hyperglycemia 3
• Avoid concomitant use of tolvaptan with strong CYP3A inhibitors (contraindicated) or moderate CYP3A inhibitors 3
• Monitor serum potassium levels during concomitant therapy with angiotensin receptor blockers, angiotensin converting enzyme inhibitors, or potassium-sparing diuretics 3

Common Pitfalls to Avoid

• Do not rely on clinical signs like skin turgor or dry mouth to assess hydration status, especially in older adults 2
• Do not use bioelectrical impedance for hydration assessment 2
• Assessment of fluid intake is often highly inaccurate in older adults, particularly in residential care settings 2
• Avoid using tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) due to risk of hepatotoxicity 3
• Patients requiring intervention to raise serum sodium urgently to prevent or treat serious neurological symptoms should not be treated with tolvaptan 3
• Pseudohyponatremia should be considered in asymptomatic patients with severe hyponatremia, particularly in conditions like multiple myeloma or chylomicronemia 4