How should hyponatraemia be evaluated and managed, including severity assessment, treatment thresholds, and prevention of over‑correction?

Management of Hyponatremia

Initial Evaluation and Severity Assessment

Hyponatremia (serum sodium <135 mmol/L) requires immediate assessment of symptom severity, volume status, and rapidity of onset to guide treatment intensity. 1

Symptom Classification

• Severe symptoms include seizures, coma, altered consciousness, confusion, delirium, or respiratory distress—these constitute a medical emergency requiring immediate hypertonic saline. 1, 2
• Moderate symptoms encompass nausea, vomiting, headache, confusion, gait instability, muscle cramps, and lethargy. 2
• Mild or asymptomatic hyponatremia may present with subtle cognitive impairment, increased fall risk (21% vs 5% in normonatremic patients), or be entirely asymptomatic. 1, 2

Volume Status Determination

• Hypovolemic hyponatremia presents with orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins, and tachycardia; urine sodium is typically <30 mmol/L. 1
• Euvolemic hyponatremia (SIADH) shows no edema, normal blood pressure, moist mucous membranes, and urine sodium >20-40 mmol/L with inappropriately concentrated urine (>300 mOsm/kg). 1
• Hypervolemic hyponatremia demonstrates peripheral edema, ascites, jugular venous distention, and pulmonary congestion, seen in heart failure and cirrhosis. 1

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Treatment of Severe Symptomatic Hyponatremia

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

Hypertonic Saline Protocol

• Give 100 mL boluses of 3% NaCl intravenously over 10 minutes, repeating up to three times at 10-minute intervals if severe symptoms persist. 1
• Check serum sodium every 2 hours during the initial correction phase to ensure safe correction rates. 1, 3
• Discontinue 3% saline once severe symptoms resolve (typically after 6 mmol/L rise), then transition to protocols for mild symptoms or asymptomatic management. 3

Critical Safety Limits

• Never exceed 8 mmol/L correction in any 24-hour period to prevent osmotic demyelination syndrome (ODS), which causes dysarthria, dysphagia, quadriparesis, seizures, or death. 1, 4, 5
• After the initial 6 mmol/L correction in 6 hours, limit additional correction to only 2 mmol/L over the remaining 18 hours. 3
• High-risk patients (advanced liver disease, chronic alcoholism, malnutrition, prior encephalopathy) require even slower correction at 4-6 mmol/L per day maximum. 1, 4

Post-Acute Management

• Switch to isotonic saline (0.9% NaCl) or fluid restriction once severe symptoms resolve and sodium reaches approximately 120-125 mmol/L. 3
• Monitor serum sodium every 4 hours (instead of every 2 hours) after symptom resolution. 3
• Implement fluid restriction to 1 L/day for SIADH once the acute phase is controlled. 3

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Treatment Based on Volume Status

Hypovolemic Hyponatremia

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/h initially, then 4-14 mL/kg/h based on clinical response, to restore intravascular volume. 1

• Discontinue diuretics immediately if sodium is <125 mmol/L. 1
• Avoid hypotonic fluids (0.45% saline, lactated Ringer's, D5W) as they worsen hyponatremia. 1
• Correction rate should not exceed 8 mmol/L in 24 hours even with volume repletion. 1

Euvolemic Hyponatremia (SIADH)

Fluid restriction to 1 L/day (or <800 mL/day for refractory cases) is the cornerstone of SIADH treatment. 1, 6

• Add oral sodium chloride 100 mEq three times daily if fluid restriction fails after 24-48 hours. 1
• Consider urea (30-60 g/day) or tolvaptan (15 mg once daily, titrate to 30-60 mg) for resistant cases, though nearly half of SIADH patients do not respond to fluid restriction alone. 1, 6
• For severe symptomatic SIADH, use 3% hypertonic saline as described above, then transition to fluid restriction. 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L, and avoid hypertonic saline unless life-threatening symptoms are present. 1

• Continue diuretics at reduced doses while closely monitoring sodium, as persistent volume overload worsens outcomes. 1
• For cirrhotic patients, add albumin infusion (8 g per liter of ascites removed) alongside fluid restriction. 1
• Temporarily discontinue diuretics if sodium drops below 125 mmol/L with concurrent renal impairment. 1
• Sodium restriction (2-2.5 g/day) is more effective than fluid restriction for weight loss in cirrhosis, as fluid passively follows sodium. 1

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Special Populations and Considerations

Neurosurgical Patients: Cerebral Salt Wasting vs. SIADH

Distinguishing cerebral salt wasting (CSW) from SIADH is critical in neurosurgical patients, as they require opposite treatments. 1

• CSW presents with hypovolemia (CVP <6 cm H₂O, orthostatic hypotension, dry mucous membranes) and requires aggressive volume and sodium replacement with isotonic or hypertonic saline. 1
• SIADH presents with euvolemia (CVP 6-10 cm H₂O, normal blood pressure) and requires fluid restriction. 1
• Never use fluid restriction in CSW or subarachnoid hemorrhage patients at risk of vasospasm, as this worsens cerebral ischemia and outcomes. 1
• Fludrocortisone (0.1-0.2 mg daily) or hydrocortisone may be added in severe CSW or subarachnoid hemorrhage to reduce renal sodium loss. 1

Cirrhotic Patients

Cirrhotic patients have exceptionally high risk of osmotic demyelination and require correction limited to 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours. 1, 4

• Hyponatremia in cirrhosis 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) and should be used with extreme caution for ≤30 days only. 1, 4
• Avoid hypertonic saline unless life-threatening symptoms are present, as it worsens ascites and edema. 1

Chronic Alcoholism and Malnutrition

Patients with chronic alcoholism, malnutrition, or advanced liver disease require slower correction (4-6 mmol/L per day) due to heightened susceptibility to osmotic demyelination. 1, 4, 7

• Even with careful correction, these patients retain a 0.5-1.5% risk of ODS. 1

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Management of Overcorrection

If serum sodium rises >8 mmol/L in 24 hours, immediately discontinue current fluids and switch to D5W (5% dextrose in water) to relower sodium levels. 1

• Administer desmopressin to slow or reverse the rapid rise in serum sodium. 1
• Target is to bring the total 24-hour correction back to ≤8 mmol/L from the starting point. 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction. 1

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Pharmacological Options

Tolvaptan (Vasopressin Receptor Antagonist)

Tolvaptan (15 mg once daily, titrate to 30-60 mg) is FDA-approved for euvolemic and hypervolemic hyponatremia but must be initiated in a hospital with close sodium monitoring. 4

• Check serum sodium every 2 hours for the first 8 hours after the initial dose to avoid overly rapid correction. 4
• Do not use for >30 days to minimize hepatotoxicity risk (4.4% developed ALT >3× ULN). 1, 4
• Avoid fluid restriction during the first 24 hours of tolvaptan to prevent overcorrection. 4
• Contraindicated in hypovolemic hyponatremia, anuria, inability to sense thirst, and with strong CYP3A inhibitors. 4

Urea

Urea (30-60 g/day) is an effective and safe second-line treatment for SIADH, particularly when fluid restriction fails. 1, 6

• Urea is preferred over vaptans in some guidelines due to lower cost and fewer adverse effects, though palatability is poor. 5, 6

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Common Pitfalls to Avoid

• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant—even mild chronic hyponatremia increases mortality 60-fold (11.2% vs 0.19%) and fall risk. 1, 2
• Correcting chronic hyponatremia faster than 8 mmol/L in 24 hours—this causes osmotic demyelination syndrome. 1, 4, 5
• Using fluid restriction in cerebral salt wasting or subarachnoid hemorrhage—this worsens outcomes and increases cerebral ischemia risk. 1
• Relying on physical examination alone for volume assessment—sensitivity is only 41%, specificity 80%; use urine sodium and osmolality. 1
• Failing to monitor sodium levels frequently during active correction—check every 2 hours for severe symptoms, every 4 hours after resolution. 1, 3
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms—this worsens fluid overload. 1
• Obtaining ADH or natriuretic peptide levels—these are not supported by evidence and delay treatment. 1

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Monitoring Protocol

• Severe symptoms: Check serum sodium every 2 hours during initial correction, then every 4 hours after symptom resolution. 1, 3
• Moderate symptoms: Check every 4-6 hours initially, then daily once stable. 1
• Asymptomatic or mild: Check every 24-48 hours initially to ensure safe correction. 1
• Monitor for osmotic demyelination syndrome signs 2-7 days after correction (dysarthria, dysphagia, quadriparesis, oculomotor dysfunction). 1