What is the approach to managing a patient with hyponatremia?

Approach to Hyponatremia

Initial Assessment and Classification

Begin by confirming true hyponatremia (serum sodium <135 mmol/L) and determining volume status through physical examination, as this fundamentally guides all subsequent management decisions. 1

Essential Initial Workup

• Obtain serum and urine osmolality, urine sodium concentration, urine electrolytes, and serum uric acid to determine the underlying cause 1
• Assess extracellular fluid volume status through physical examination: look for orthostatic hypotension, dry mucous membranes, decreased skin turgor (hypovolemic); peripheral edema, ascites, jugular venous distention (hypervolemic); or absence of these findings (euvolemic) 1, 2
• Measure serum osmolality to exclude pseudohyponatremia (normal osmolality) or hyperglycemia-induced hyponatremia (high osmolality) 3
• Check thyroid function (TSH) and consider cortisol to rule out hypothyroidism and adrenal insufficiency 1

Volume Status Classification

• Hypovolemic hyponatremia: Urine sodium <30 mmol/L suggests extrarenal losses (GI losses, burns, dehydration); urine sodium >20 mmol/L suggests renal losses (diuretics, salt-wasting nephropathy) 1
• Euvolemic hyponatremia: Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg strongly suggests SIADH (serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH) 1
• Hypervolemic hyponatremia: Presence of edema, ascites, or signs of heart failure/cirrhosis with total body sodium and water excess 1

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Critical Correction Rate Guidelines

The single most important safety principle: never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome, regardless of the treatment modality used. 1, 2

Standard Correction Rates

• Average-risk patients: 4-8 mmol/L per day, maximum 10-12 mmol/L in 24 hours 1
• High-risk patients (advanced liver disease, alcoholism, malnutrition, severe hyponatremia, prior encephalopathy): 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1, 2
• Chronic hyponatremia (>48 hours or unknown duration): Avoid correction exceeding 1 mmol/L/hour 1

Monitoring Frequency

• Severe symptoms: Check serum sodium every 2 hours during initial correction 1, 4
• Mild symptoms or asymptomatic: Check every 4 hours initially, then every 24 hours once stable 1

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Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Medical Emergency)

For patients with seizures, coma, altered mental status, or cardiorespiratory distress, immediately administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until symptoms resolve. 1, 5

• Administer 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to three times at 10-minute intervals until symptoms improve 1
• Goal: Increase sodium by 4-6 mmol/L within 1-2 hours to reverse hyponatremic encephalopathy 5
• Critical limit: Total correction must not exceed 8 mmol/L in 24 hours (if 6 mmol/L corrected in first 6 hours, only 2 mmol/L additional allowed in next 18 hours) 1, 4
• Requires ICU admission with continuous monitoring 1

Mild to Moderate Symptomatic or Asymptomatic Hyponatremia

Treatment depends entirely on volume status (see below sections).

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Treatment Based on Volume Status

Hypovolemic Hyponatremia

Discontinue diuretics immediately and administer isotonic saline (0.9% NaCl) for volume repletion. 1, 2

• Initial infusion rate: 15-20 mL/kg/h for first hour, then 4-14 mL/kg/h based on clinical response 1
• Urine sodium <30 mmol/L predicts good response to saline (71-100% positive predictive value) 1
• For cirrhotic patients: Consider albumin infusion alongside isotonic saline, with more cautious correction (4-6 mmol/L per day) 1
• Once euvolemic, switch to maintenance fluids and reassess 1

Euvolemic Hyponatremia (SIADH)

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

• First-line: Fluid restriction to 1000 mL/day for mild/asymptomatic cases 1
• Second-line: If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• Pharmacological options for resistant cases:
  • Urea (effective but poor palatability) 5
  • Tolvaptan 15 mg once daily, titrate to 30-60 mg (use with extreme caution; see below) 6
  • Demeclocycline or lithium (less commonly used due to side effects) 1
• For severe symptoms: Use 3% hypertonic saline as described above 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Implement fluid restriction to 1000-1500 mL/day for serum sodium <125 mmol/L. 1, 2

• Discontinue or temporarily hold diuretics if sodium <125 mmol/L 1
• For cirrhosis: Consider albumin infusion (6-8 g per liter of ascites drained) alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms present, as it worsens edema and ascites 1
• Sodium restriction (2-2.5 g/day) is more important than fluid restriction for weight loss, as fluid passively follows sodium 1
• Vaptans (tolvaptan) may be considered for persistent severe hyponatremia despite fluid restriction and maximized guideline-directed therapy, but use with extreme caution in cirrhosis due to 10% risk of GI bleeding vs. 2% with placebo 1, 6

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Special Considerations: Neurosurgical Patients

In neurosurgical patients, distinguishing SIADH from cerebral salt wasting (CSW) is critical, as they require opposite treatments. 1, 4

SIADH Characteristics

• Euvolemic or slight hypervolemia 4
• Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg 1
• Treatment: Fluid restriction to 1 L/day 1, 4

Cerebral Salt Wasting Characteristics

• True hypovolemia with evidence of volume depletion (hypotension, tachycardia, dry mucous membranes, CVP <6 cm H₂O) 1, 4
• High urine sodium >20 mmol/L despite volume depletion 1
• More common in poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 1

CSW Treatment

• Volume and sodium replacement with isotonic or hypertonic saline (NOT fluid restriction) 1, 4
• For severe symptoms: 3% hypertonic saline plus fludrocortisone 0.1-0.2 mg daily in ICU 1, 4
• Consider hydrocortisone to prevent natriuresis in subarachnoid hemorrhage patients 1
• Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm, as this worsens outcomes 1, 4

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Tolvaptan Use: Specific Guidelines

Tolvaptan should be initiated in hospital to monitor for overly rapid correction and requires discontinuation after 30 days maximum to minimize liver injury risk. 6

Dosing

• Start 15 mg once daily, increase to 30 mg after at least 24 hours, maximum 60 mg daily as needed 6
• Avoid fluid restriction during first 24 hours; patients can drink to thirst 6
• Upon discontinuation, resume fluid restriction and monitor sodium closely 6

Contraindications and Cautions

• Contraindicated with strong CYP3A inhibitors (ketoconazole increases tolvaptan AUC 5.4-fold) 6
• Avoid with moderate CYP3A inhibitors and grapefruit juice 6
• Use with extreme caution in cirrhosis: 10% GI bleeding risk vs. 2% placebo, and increased mortality with long-term use 6
• Monitor for hyperkalemia when used with ACE inhibitors, ARBs, or potassium-sparing diuretics 6
• Risk of overly rapid correction and osmotic demyelination syndrome 6

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Common Pitfalls to Avoid

• Never ignore mild hyponatremia (130-135 mmol/L) as clinically insignificant—it increases fall risk (21% vs. 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L) 1, 5
• Never use fluid restriction in cerebral salt wasting—this worsens outcomes and can precipitate cerebral ischemia 1, 4
• Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours—osmotic demyelination syndrome can cause irreversible dysarthria, dysphagia, quadriparesis, or death 1, 2, 5
• Never use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms—it worsens fluid overload 1
• Never fail to identify and treat the underlying cause—symptomatic management alone is insufficient 1
• Never rely on physical examination alone for volume assessment—sensitivity is only 41.1% and specificity 80% 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
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically appearing 2-7 days after rapid correction 1, 2