What are the treatment options for correcting hyponatremia?

Hyponatremia Assessment and Correction

Initial Assessment

Hyponatremia (serum sodium <135 mmol/L) requires systematic evaluation based on volume status, serum osmolality, symptom severity, and onset timing to guide appropriate treatment. 1

Diagnostic Workup

• Obtain serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and assess extracellular fluid volume status 1
• Check serum creatinine, electrolytes (potassium, calcium, magnesium), thyroid-stimulating hormone, and liver function tests 1
• Measure serum glucose to exclude pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1
• Urine sodium <30 mmol/L predicts response to 0.9% saline with 71-100% positive predictive value 1
• Serum uric acid <4 mg/dL suggests SIADH with 73-100% positive predictive value 1

Volume Status Classification

• Hypovolemic: Orthostatic hypotension, dry mucous membranes, decreased skin turgor, urine sodium typically <30 mmol/L 1
• Euvolemic: No edema, normal blood pressure, normal skin turgor, moist mucous membranes 1
• Hypervolemic: Peripheral edema, ascites, jugular venous distention, pulmonary congestion 1

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Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with seizures, coma, altered consciousness, or cardiorespiratory distress, immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until severe symptoms resolve. 1

• Give 3% hypertonic saline as 100-150 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1
• Never exceed 8 mmol/L total correction in 24 hours to prevent osmotic demyelination syndrome 1, 2
• Monitor serum sodium every 2 hours during initial correction 1
• Once severe symptoms resolve, discontinue 3% saline and transition to protocols for mild symptoms 3
• After initial 6 mmol/L correction, limit additional correction to only 2 mmol/L in the following 18 hours 3

Mild to Moderate Symptomatic or Asymptomatic Hyponatremia

Treatment depends on volume status:

Hypovolemic Hyponatremia

• Discontinue diuretics immediately 1
• Administer isotonic saline (0.9% NaCl) for volume repletion 1
• Correction rate should not exceed 8 mmol/L in 24 hours 1

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of treatment 1
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• For resistant cases, consider vasopressin receptor antagonists (tolvaptan 15 mg once daily, titrate to 30-60 mg) 1, 2
• Alternative options include urea, demeclocycline, or lithium 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

• Implement fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1
• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• Consider albumin infusion in cirrhotic patients 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens edema and ascites 1
• Vasopressin receptor antagonists may be considered for persistent severe hyponatremia despite fluid restriction 1, 2

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Critical Correction Rate Guidelines

Standard Correction Rates

• Maximum correction: 8 mmol/L in 24 hours for most patients 1, 2
• For severe symptoms: 6 mmol/L over first 6 hours, then limit to 2 mmol/L over next 18 hours 1
• Chronic hyponatremia (>48 hours): avoid correction >1 mmol/L/hour 1

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

Patients with advanced liver disease, alcoholism, malnutrition, severe hyponatremia, or prior encephalopathy require more cautious correction at 4-6 mmol/L per day, not exceeding 8 mmol/L in 24 hours. 1, 2

• These patients have significantly higher risk of osmotic demyelination syndrome 1
• Monitor sodium levels every 2-4 hours during active correction 1

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Special Considerations

Neurosurgical Patients (Cerebral Salt Wasting vs. SIADH)

In neurosurgical patients, distinguishing cerebral salt wasting (CSW) from SIADH is critical because treatments are opposite. 1

• CSW: Treat with volume and sodium replacement (isotonic or hypertonic saline), NOT fluid restriction 1
  • Add fludrocortisone 0.1-0.2 mg daily for severe symptoms 1
  • Consider hydrocortisone to prevent natriuresis 1
• SIADH: Treat with fluid restriction 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1

Cirrhotic Patients

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

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Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours, immediately intervene to prevent osmotic demyelination syndrome. 1

• Discontinue current fluids and switch to D5W (5% dextrose in water) 1
• Consider administering desmopressin to slow or reverse the rapid rise 1
• Monitor for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1, 2

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Pharmacological Options

Vasopressin Receptor Antagonists (Vaptans)

Tolvaptan is indicated for clinically significant euvolemic or hypervolemic hyponatremia (serum sodium <125 mEq/L or symptomatic hyponatremia resistant to fluid restriction). 2

• Must initiate and re-initiate in hospital with close sodium monitoring 2
• Starting dose: 15 mg once daily, titrate to 30-60 mg based on response 2
• Avoid fluid restriction during first 24 hours of tolvaptan therapy 2
• Do not use for more than 30 days due to hepatotoxicity risk 2
• Contraindicated in hypovolemic hyponatremia, anuria, and with strong CYP3A inhibitors 2
• In clinical trials, tolvaptan increased serum sodium by 4.0 mEq/L at Day 4 vs. 0.4 mEq/L with placebo (p<0.0001) 2

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Common Pitfalls to Avoid

• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant—it increases fall risk (21% vs. 5%) and mortality (60-fold increase for sodium <130 mmol/L) 1, 4
• Overly rapid correction exceeding 8 mmol/L in 24 hours leading to osmotic demyelination syndrome 1, 2
• Using fluid restriction in cerebral salt wasting—this worsens outcomes 1
• Inadequate monitoring during active correction 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Failing to recognize and treat the underlying cause 1