What is the treatment approach for patients presenting with hyponatremia (low sodium levels)?

Treatment Approach for Hyponatremia

The treatment of hyponatremia must be guided by three critical factors: symptom severity, volume status (hypovolemic, euvolemic, or hypervolemic), and chronicity, with the overriding principle that correction must never exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1

Initial Assessment and Classification

Determine Symptom Severity

• Severe symptoms (seizures, coma, altered mental status, cardiorespiratory distress) require immediate hypertonic saline regardless of sodium level 1, 2
• Mild symptoms (nausea, vomiting, headache, weakness) allow for more conservative management 3
• Asymptomatic patients can be managed based on volume status and underlying cause 1

Assess Volume Status

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1
• Euvolemic: no edema, normal blood pressure, normal skin turgor 1
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention 1

Obtain Essential Laboratory Tests

• Serum and urine osmolality 1
• Urine sodium concentration (spot urine sodium <30 mmol/L predicts 71-100% response to saline) 1
• Serum uric acid (<4 mg/dL suggests SIADH with 73-100% positive predictive value) 1
• Thyroid function and cortisol to exclude endocrine causes 1

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

Administer 3% hypertonic saline immediately with a target correction of 6 mmol/L over 6 hours or until severe symptoms resolve. 1, 2

• Give 100-150 mL boluses of 3% saline over 10 minutes, repeatable up to three times at 10-minute intervals 1
• Critical safety limit: Total correction must not exceed 8 mmol/L in 24 hours 1, 4
• Monitor serum sodium every 2 hours during initial correction 1
• Once 6 mmol/L is corrected in 6 hours, only 2 mmol/L additional correction is allowed in the next 18 hours 1

Mild Symptomatic or Asymptomatic Hyponatremia

Treatment depends on volume status and underlying cause 1

Treatment Based on Volume Status

Hypovolemic Hyponatremia

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

• Initial infusion rate: 15-20 mL/kg/h, then 4-14 mL/kg/h based on response 1
• Urine sodium <30 mmol/L predicts good response to saline (71-100% positive predictive value) 1
• Correction rate must not exceed 8 mmol/L in 24 hours 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day is the cornerstone of first-line treatment. 1

• If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 1, 5
• For persistent cases despite fluid restriction, consider:
  • Urea (effective second-line option with good safety profile) 1, 6
  • Tolvaptan 15 mg once daily, titrated to 30-60 mg as needed (FDA-approved vaptan) 4
• Avoid fluid restriction in neurosurgical patients with subarachnoid hemorrhage at risk for vasospasm 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

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

• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• For cirrhotic patients, consider albumin infusion alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema 1
• Tolvaptan may be considered for persistent severe hyponatremia despite fluid restriction, but use with extreme caution in cirrhosis due to higher risk of gastrointestinal bleeding (10% vs 2% placebo) 1, 4

Special Populations and High-Risk Considerations

Patients at High Risk for Osmotic Demyelination Syndrome

Patients with advanced liver disease, alcoholism, malnutrition, or prior encephalopathy require even more cautious correction at 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours. 1

Neurosurgical Patients: Distinguishing SIADH from Cerebral Salt Wasting (CSW)

This distinction is critical as treatments are opposite 1:

• SIADH: Euvolemic, treat with fluid restriction 1
• CSW: Hypovolemic (CVP <6 cm H₂O), treat with volume and sodium replacement with normal saline or hypertonic saline 1
• Never use fluid restriction in CSW as it worsens outcomes 1
• Consider fludrocortisone 0.1-0.2 mg daily for severe CSW or subarachnoid hemorrhage patients 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
• Correction rate must be limited to 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1
• Sodium restriction (not fluid restriction) results in weight loss as fluid follows sodium 1

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours, 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
• Monitor for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1, 4

Monitoring During Treatment

• Severe symptoms: Check serum sodium every 2 hours during initial correction 1
• Mild symptoms: Check every 4-6 hours initially, then daily 1
• Track daily weight and fluid balance meticulously 1
• Watch for signs of overcorrection or osmotic demyelination syndrome 1

Common Pitfalls to Avoid

• Never exceed 8 mmol/L correction in 24 hours for chronic hyponatremia—this causes osmotic demyelination syndrome 1, 4
• Never use fluid restriction in cerebral salt wasting—it worsens outcomes 1
• Never use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms—it worsens fluid overload 1
• Never ignore mild hyponatremia (130-135 mmol/L)—it increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1, 2
• Inadequate monitoring during active correction can lead to osmotic demyelination syndrome 1
• Failing to recognize and treat the underlying cause leads to recurrence 1

Pharmacological Options Summary

Tolvaptan (FDA-Approved Vaptan)

• Indication: Euvolemic or hypervolemic hyponatremia (serum sodium <125 mEq/L or symptomatic) 4
• Dosing: Start 15 mg once daily, titrate to 30-60 mg as needed 4
• Must be initiated in hospital with close sodium monitoring 4
• Maximum duration: 30 days to minimize liver injury risk 4
• Contraindications: Hypovolemic hyponatremia, anuria, strong CYP3A inhibitors, inability to sense thirst 4
• Avoid fluid restriction during first 24 hours of tolvaptan therapy 4

Oral Sodium Chloride

• Dosing: 100 mEq three times daily for SIADH not responding to fluid restriction 1, 5
• Combine with fluid restriction to 1 L/day 5
• Monitor for hyperkalemia, especially in patients with renal impairment 5