What is the treatment for hyponatremia (low sodium levels)?

Treatment of Hyponatremia

The treatment of hyponatremia depends critically on symptom severity, volume status, and rapidity of onset, with severe symptomatic cases requiring immediate 3% hypertonic saline and asymptomatic cases managed primarily through addressing the underlying cause and fluid restriction. 1

Initial Assessment

Before initiating treatment, determine three key factors:

• Symptom severity: Severe symptoms include seizures, coma, altered mental status, or cardiorespiratory distress; mild symptoms include nausea, vomiting, headache, or weakness 1, 2
• Volume status: Classify as hypovolemic (dehydration, orthostatic hypotension, dry mucous membranes), euvolemic (normal volume status), or hypervolemic (edema, ascites, jugular venous distension) 1, 3
• Acuity: Acute (<48 hours) versus chronic (>48 hours) onset 1
• Serum osmolality and urine studies: Check serum and urine osmolality, urine sodium, and urine electrolytes to determine the underlying cause 1

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with seizures, coma, confusion, or severe neurological symptoms, immediately administer 3% hypertonic saline regardless of the serum sodium level. 1, 3

• Administer 100-150 mL bolus of 3% hypertonic saline over 10 minutes, which can be repeated up to three times at 10-minute intervals until symptoms improve 1
• Target correction: Increase sodium by 4-6 mEq/L over the first 6 hours or until severe symptoms resolve 1, 3
• Monitor serum sodium every 2 hours during initial correction 1
• Maximum correction limit: Do not exceed 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 1, 4, 2

Asymptomatic or Mildly Symptomatic Hyponatremia

Treatment is based on volume status and underlying cause 1, 3:

Hypovolemic Hyponatremia

• Discontinue diuretics immediately 1
• Administer 0.9% normal saline for volume repletion 1, 3
• Urinary sodium <30 mmol/L predicts response to saline with 71-100% positive predictive value 1

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of first-line treatment 1, 5
• If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 1
• Second-line pharmacological options for resistant cases:
  • Urea 15-30 g/day (highly effective and safe) 1, 6
  • Tolvaptan 15 mg once daily, titrated to 30-60 mg as needed (FDA-approved vaptan) 4
  • Demeclocycline or lithium (less commonly used due to side effects) 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

• Fluid restriction to 1-1.5 L/day for serum sodium <125 mEq/L 1, 3
• Treat the underlying condition (optimize heart failure management, manage cirrhosis) 1, 7
• Consider albumin infusion in cirrhotic patients 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it may worsen edema and ascites 1
• Discontinue diuretics temporarily if sodium <125 mEq/L 1

Correction Rate Guidelines (Critical Safety Parameters)

The single most important safety consideration is avoiding overly rapid correction, which causes osmotic demyelination syndrome. 1, 4, 2

Standard Correction Limits

• Maximum 8 mEq/L increase in 24 hours for most patients 1, 4, 3
• Maximum 12 mEq/L increase in 24 hours is the absolute upper limit per FDA guidelines 4

High-Risk Patients Requiring Slower Correction (4-6 mEq/L per day)

Patients with the following conditions are at increased risk for osmotic demyelination syndrome and require more cautious correction 1, 4:

• Advanced liver disease or cirrhosis
• Chronic alcoholism
• Severe malnutrition
• Hypokalemia or hypophosphatemia
• Prior history of encephalopathy

Special Populations and Considerations

Neurosurgical Patients (Cerebral Salt Wasting vs. SIADH)

In neurosurgical patients, cerebral salt wasting (CSW) is more common than SIADH and requires fundamentally different treatment. 1

• CSW treatment: Volume and sodium replacement with isotonic or hypertonic saline, plus fludrocortisone 0.1-0.2 mg daily 1
• Never use fluid restriction in CSW, as it worsens outcomes 1
• Distinguish CSW from SIADH: CSW presents with evidence of volume depletion (hypotension, tachycardia, dry mucous membranes), while SIADH is euvolemic 1
• In subarachnoid hemorrhage patients at risk for vasospasm, avoid fluid restriction and consider fludrocortisone 1

Cirrhotic Patients

• Hyponatremia in cirrhosis increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Sodium restriction (not fluid restriction) is more effective for weight loss, as fluid passively follows sodium 1
• Tolvaptan carries higher risk of gastrointestinal bleeding in cirrhosis (10% vs. 2% placebo) 1

Management of Overcorrection

If sodium correction exceeds 8 mEq/L in 24 hours, immediate intervention is required to prevent osmotic demyelination syndrome. 1

• Immediately discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Administer desmopressin to slow or reverse the rapid rise in serum sodium 1
• Target: Bring total 24-hour correction to no more than 8 mEq/L from the starting point 1
• Monitor for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1, 4

Pharmacological Agents

Tolvaptan (Vasopressin Receptor Antagonist)

Tolvaptan is FDA-approved for euvolemic and hypervolemic hyponatremia with serum sodium <125 mEq/L or symptomatic hyponatremia resistant to fluid restriction. 4

• Dosing: Start 15 mg once daily, titrate to 30 mg then 60 mg at 24-hour intervals as needed 4
• Must be initiated in hospital with close serum sodium monitoring 4
• Avoid use >30 days due to hepatotoxicity risk 4
• Contraindicated in hypovolemic hyponatremia, anuria, inability to sense thirst, and with strong CYP3A inhibitors 4
• Increases serum sodium significantly more than placebo, with effects seen as early as 8 hours 4

Urea

• Dose: 15-30 g/day orally 6
• Highly effective and safe for SIADH 1, 6
• Adverse effects include poor palatability and gastric intolerance 2

Common Pitfalls to Avoid

• Overly rapid correction (>8 mEq/L in 24 hours) leading to osmotic demyelination syndrome 1, 4, 2
• Using fluid restriction in cerebral salt wasting, which worsens outcomes 1
• Inadequate monitoring during active correction 1
• Ignoring mild hyponatremia (130-135 mEq/L), which increases fall risk and mortality 1, 2
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Failing to distinguish between SIADH and cerebral salt wasting in neurosurgical patients 1
• Administering normal saline to SIADH patients, which may worsen hyponatremia 1

Monitoring Requirements

• Severe symptoms: Check serum sodium every 2 hours during initial correction 1
• After symptom resolution: Check every 4 hours, then daily 1
• During tolvaptan therapy: Frequent monitoring required, especially in first 24-48 hours 4
• Track daily weight in hypervolemic patients (aim for 0.5 kg/day loss without peripheral edema) 1