What are the treatment options for hyponatremia?

Treatment of Hyponatremia

Initial Assessment and Classification

Treatment of hyponatremia must be guided by symptom severity, volume status, and correction rate limits to prevent osmotic demyelination syndrome while addressing the underlying cause. 1

Begin by determining:

• Symptom severity: Severe symptoms (seizures, coma, altered mental status) vs. mild/asymptomatic 1
• Volume status: Hypovolemic, euvolemic, or hypervolemic 1, 2
• Chronicity: Acute (<48 hours) vs. chronic (>48 hours) 1
• Serum sodium level: Mild (130-135 mEq/L), moderate (125-129 mEq/L), or severe (<125 mEq/L) 3

Essential initial workup includes serum and urine osmolality, urine sodium, urine electrolytes, serum uric acid, and assessment of extracellular fluid volume status 1. A urine sodium <30 mmol/L predicts response to saline with 71-100% positive predictive value, while serum uric acid <4 mg/dL suggests SIADH with 73-100% positive predictive value 1.

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with severe symptoms (seizures, coma, confusion, altered mental status), immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve. 1, 2, 3

• Administer 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1
• Critical safety limit: Total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 2, 4
• Monitor serum sodium every 2 hours during initial correction 1
• Consider ICU admission for close monitoring 1

Mild to Moderate Symptomatic or Asymptomatic Hyponatremia

Treatment depends on volume status and underlying etiology 1, 3.

Treatment Based on Volume Status

Hypovolemic Hyponatremia

Discontinue diuretics and administer isotonic saline (0.9% NaCl) for volume repletion. 1, 3

• Initial infusion rate: 15-20 mL/kg/h, then 4-14 mL/kg/h based on response 1
• Urine sodium <30 mmol/L indicates extrarenal losses (GI losses, burns, dehydration) 1
• Urine sodium >20 mmol/L suggests renal losses (diuretics, salt-wasting nephropathy) 1
• Continue isotonic fluids until euvolemia is achieved 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of treatment for SIADH. 1, 2, 3

• Implement strict fluid restriction to <1000 mL/day 1
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• For persistent cases despite fluid restriction, consider vasopressin receptor antagonists (tolvaptan 15 mg once daily, titrate to 30-60 mg) 1, 5
• Alternative pharmacological options include urea, demeclocycline, or lithium (less commonly used due to side effects) 1, 2

Important distinction: In neurosurgical patients, cerebral salt wasting (CSW) is more common than SIADH and requires fundamentally different treatment 1. CSW is characterized by true hypovolemia with high urine sodium despite volume depletion, and requires volume and sodium replacement—never fluid restriction 1.

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L. 1, 3, 6

• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• For cirrhotic patients, consider albumin infusion (6-8 g per liter of ascites drained) alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema 1
• Sodium restriction (2-2.5 g/day or 88-110 mmol/day) is more important than fluid restriction for weight loss, as fluid passively follows sodium 1
• For persistent severe hyponatremia despite fluid restriction and maximized guideline-directed medical therapy, consider tolvaptan with extreme caution 1, 5

Critical Correction Rate Guidelines

The maximum correction rate must not exceed 8 mmol/L in 24 hours for most patients. 1, 2, 4, 3

Standard correction rates:

• Average-risk patients: 4-8 mmol/L per day, not exceeding 10-12 mmol/L in 24 hours 1
• High-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy, severe hyponatremia): 4-6 mmol/L per day, not exceeding 8 mmol/L in 24 hours 1, 2
• Chronic hyponatremia: Avoid correction faster than 1 mmol/L/hour 1

Calculate sodium deficit using: Desired increase in Na (mEq/L) × (0.5 × ideal body weight in kg) 1

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours 1:

• Immediately discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Consider administering desmopressin to slow or reverse the rapid rise 1
• Target reduction to bring total 24-hour correction to no more than 8 mmol/L from starting point 1

Pharmacological Options

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan is FDA-approved for euvolemic or hypervolemic hyponatremia, with significant efficacy but requires careful monitoring. 5, 2

• Starting dose: 15 mg once daily, titrate to 30 mg then 60 mg based on response 5
• Avoid fluid restriction during first 24 hours to prevent overly rapid correction 5
• Monitor serum sodium at 8 hours, then daily for first 72 hours 5
• Contraindicated with strong CYP3A inhibitors (ketoconazole increases tolvaptan AUC 5.4-fold) 5
• Use with extreme caution in cirrhosis: 10% risk of GI bleeding vs. 2% with placebo 1, 5
• Side effects include thirst, dry mouth, polyuria, and risk of overly rapid correction 5, 7

Urea

Urea is an effective alternative for SIADH management 1, 2:

• Dose: 40 g in 100-150 mL normal saline every 8 hours for 1-2 days in neurosurgical patients 1
• Side effects include poor palatability and gastric intolerance 2

Special Populations and Considerations

Neurosurgical Patients

Distinguish between SIADH and cerebral salt wasting (CSW), as treatment approaches are opposite. 1

• CSW treatment: Volume and sodium replacement with isotonic or hypertonic saline, fludrocortisone for severe cases 1
• Never use fluid restriction in CSW—this worsens outcomes 1
• In subarachnoid hemorrhage patients at risk of vasospasm, avoid fluid restriction and consider fludrocortisone or hydrocortisone 1

Cirrhotic Patients

Hyponatremia in cirrhosis increases risk of 1:

• Spontaneous bacterial peritonitis (OR 3.40)
• Hepatorenal syndrome (OR 3.45)
• Hepatic encephalopathy (OR 2.36)

Require more cautious correction (4-6 mmol/L per day) due to higher risk of osmotic demyelination syndrome. 1

Patients on Diuretics

For mild hyponatremia (126-135 mmol/L) with normal creatinine 1:

• Continue diuretic therapy with close electrolyte monitoring
• Water restriction not recommended at this level
• For sodium 121-125 mmol/L, consider more cautious approach
• For sodium ≤120 mmol/L, stop diuretics and consider volume expansion

Common Pitfalls to Avoid

• Overly rapid correction (>8 mmol/L in 24 hours) leading to osmotic demyelination syndrome 1, 2, 4
• Inadequate monitoring during active correction 1
• Using fluid restriction in CSW, which worsens outcomes 1
• Failing to recognize and treat the underlying cause 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Ignoring mild hyponatremia (130-135 mmol/L), which increases fall risk (21% vs. 5%) and mortality 1, 2
• Using normal saline for SIADH or hypervolemic hyponatremia, which can worsen hyponatremia 1

Monitoring Requirements

• Severe symptoms: Check serum sodium every 2 hours during initial correction 1
• After symptom resolution: Check every 4 hours 1
• Stable patients: Daily monitoring until target reached 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1