What are the classifications, diagnosis, and treatment options for hyponatremia?

Hyponatremia Classification, Diagnosis, and Treatment

Classification of Hyponatremia

Hyponatremia is defined as serum sodium <135 mEq/L and is classified by severity, volume status, and symptom acuity. 1

By Severity

• Mild: 130-135 mEq/L 1
• Moderate: 120-125 mEq/L 1
• Severe: <120 mEq/L 1

By Volume Status

• Hypovolemic: Decreased extracellular fluid volume with signs of dehydration (orthostatic hypotension, dry mucous membranes, decreased skin turgor) 1, 2
• Euvolemic: Normal volume status without edema or signs of dehydration 1, 2
• Hypervolemic: Volume overload with edema, ascites, or jugular venous distention (seen in heart failure, cirrhosis, renal disease) 1, 3

By Acuity

• Acute: <48 hours duration 1
• Chronic: >48 hours duration 1

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Diagnostic Approach

The initial workup must include serum and urine osmolality, urine sodium, uric acid, and clinical assessment of extracellular fluid volume status. 1

Step 1: Confirm True Hyponatremia

• Measure serum osmolality (normal: 275-290 mOsm/kg) to rule out pseudohyponatremia from hyperglycemia, hypertriglyceridemia, or laboratory error 1, 2

Step 2: Assess Volume Status

• Physical examination for orthostatic hypotension, mucous membrane moisture, skin turgor, edema, ascites, and jugular venous distention 1, 2
• Note: Physical examination alone has limited accuracy (sensitivity 41.1%, specificity 80%) 2

Step 3: Measure Urine Studies

• Urine osmolality:

  • 100 mOsm/kg suggests SIADH or other causes of impaired water excretion 1, 2

  • <100 mOsm/kg suggests primary polydipsia 1

• Urine sodium:

  • <30 mEq/L: Suggests extrarenal losses (hypovolemic) or low effective circulating volume (hypervolemic) 1, 2

  • 20-40 mEq/L: Suggests renal losses, SIADH, cerebral salt wasting, or diuretic use 1, 2

Step 4: Additional Tests

• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH (though may also occur in cerebral salt wasting) 1, 2
• Thyroid-stimulating hormone (TSH) to rule out hypothyroidism 1
• Cortisol level if adrenal insufficiency suspected 1
• Do NOT routinely measure ADH or natriuretic peptide levels (not supported by evidence) 2

Diagnostic Algorithm by Volume Status

Hypovolemic Hyponatremia:

• Urine sodium <30 mEq/L → Extrarenal losses (vomiting, diarrhea, burns, third-spacing) 1, 2
• Urine sodium >20 mEq/L → Renal losses (diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy) 1, 2

Euvolemic Hyponatremia:

• Urine osmolality >100 mOsm/kg + urine sodium >40 mEq/L → SIADH 1, 2
• Rule out hypothyroidism, adrenal insufficiency, and medications 1

Hypervolemic Hyponatremia:

• Heart failure, cirrhosis, nephrotic syndrome, or advanced renal failure 1, 3
• Urine sodium typically <30 mEq/L unless on diuretics 1

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Treatment Approach

Critical Safety Principle

The maximum correction rate is 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1, 4 High-risk patients (advanced liver disease, alcoholism, malnutrition) require even slower correction at 4-6 mmol/L per day. 1

Treatment Based on Symptom Severity

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

This is a medical emergency requiring immediate treatment with 3% hypertonic saline. 1, 5

• Administer 100 mL of 3% hypertonic saline IV bolus over 10 minutes 1
• Can repeat up to 3 times at 10-minute intervals until symptoms improve 1
• Target: Increase sodium by 4-6 mEq/L over first 1-2 hours or until symptoms resolve 1, 5
• Monitor serum sodium every 2 hours during initial correction 1
• Do not exceed 8 mmol/L correction in 24 hours (or 6 mmol/L in high-risk patients) 1, 4
• ICU admission recommended for close monitoring 1

Moderate Symptomatic Hyponatremia (Nausea, Confusion, Headache)

• Consider 3% hypertonic saline with slower infusion rate 1
• Target correction: 4-6 mEq/L over 6 hours 1
• Monitor sodium every 4 hours initially 1

Asymptomatic or Mild Hyponatremia

Treatment depends on volume status and underlying cause 1

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Treatment Based on Volume Status

Hypovolemic Hyponatremia

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

• For severe dehydration with neurological symptoms: Consider hypertonic saline with careful monitoring 1
• Once euvolemic: Reassess and adjust therapy based on sodium response 1
• Correction rate: Do 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

• Mild/asymptomatic cases:

  • Fluid restriction to 1 L/day 1
  • If no response, add oral sodium chloride 100 mEq three times daily 1

• Second-line pharmacological options:

  • Urea: Effective and safe; dose 40 g in 100-150 mL normal saline every 8 hours 1
  • Tolvaptan (vaptan): Start 15 mg once daily, titrate to 30-60 mg as needed 4
    • FDA Warning: Must initiate in hospital with close sodium monitoring 4
    • Contraindicated with strong CYP3A inhibitors 4
    • Maximum duration: 30 days to minimize liver injury risk 4
  • Demeclocycline or lithium: Less commonly used due to side effects 1

• Severe symptomatic SIADH: 3% hypertonic saline as above 1

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

Fluid restriction to 1-1.5 L/day for sodium <125 mEq/L is the primary approach. 1

• Discontinue diuretics temporarily if sodium <125 mEq/L 1
• For cirrhosis: Consider albumin infusion alongside fluid restriction 1
• Sodium restriction (2-2.5 g/day or 88-110 mmol/day) is more important than fluid restriction for weight loss 1
• Avoid hypertonic saline unless life-threatening symptoms present (worsens edema and ascites) 1
• Vaptans may be considered for persistent severe hyponatremia despite fluid restriction, but use with extreme caution in cirrhosis due to increased GI bleeding risk (10% vs 2% placebo) 1

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Special Considerations

Cerebral Salt Wasting (CSW) in Neurosurgical Patients

CSW requires volume and sodium replacement, NOT fluid restriction. 1

• Treatment: Isotonic or hypertonic saline based on severity 1
• For severe symptoms: 3% hypertonic saline plus fludrocortisone 1
• Hydrocortisone may prevent natriuresis in subarachnoid hemorrhage patients 1
• Critical distinction: CSW shows hypovolemia (CVP <6 cm H₂O) while SIADH shows euvolemia (CVP 6-10 cm H₂O) 2
• Avoid fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm 1

Overcorrection Management

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
• Administer desmopressin to slow or reverse rapid sodium rise 1
• Target: Bring total 24-hour correction to ≤8 mmol/L from baseline 1
• Monitor for osmotic demyelination signs: Dysarthria, dysphagia, oculomotor dysfunction, quadriparesis (typically 2-7 days post-correction) 1

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Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours leads to osmotic demyelination syndrome 1, 4
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting 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 mEq/L) as clinically insignificant—it increases fall risk (21% vs 5%) and mortality (60-fold increase when <130 mEq/L) 1, 5
• Relying solely on physical examination to determine volume status 2
• Administering normal saline to SIADH patients worsens hyponatremia 1