How to approach hyponatremia?

Approach to Hyponatremia

Hyponatremia (serum sodium <135 mmol/L) requires systematic evaluation based on volume status, symptom severity, and chronicity, with treatment prioritizing prevention of both cerebral edema from severe hyponatremia and osmotic demyelination syndrome from overly rapid correction. 1

Initial Assessment and Classification

Define Severity and Acuity

• Mild: 130-135 mmol/L 1
• Moderate: 120-125 mmol/L 1
• Severe: <120 mmol/L 1
• Acute: <48 hours duration 1, 2
• Chronic: >48 hours or unknown duration 1, 2

Essential Laboratory Workup

• Serum osmolality to exclude pseudohyponatremia (hyperglycemia, hyperlipidemia) 1, 2
• Urine osmolality and urine sodium concentration 1, 2
• Serum creatinine, BUN, glucose, TSH, and cortisol to exclude secondary causes 1
• Uric acid (serum uric acid <4 mg/dL suggests SIADH with 73-100% positive predictive value) 1

Do not obtain ADH or natriuretic peptide levels as they are not supported by evidence and delay treatment 1

Volume Status Assessment

Perform careful physical examination looking for: 1, 2

• Hypovolemia: Orthostatic hypotension, dry mucous membranes, poor skin turgor, flat neck veins
• Euvolemia: Normal vital signs, no edema, moist mucous membranes
• Hypervolemia: Jugular venous distension, peripheral edema, ascites, pulmonary crackles

Diagnostic Algorithm Based on Urine Studies

Hypotonic Hyponatremia (Serum Osm <280 mOsm/kg)

Urine Osmolality <100 mOsm/kg: 2

• Primary polydipsia
• Beer potomania (treat by discontinuing alcohol and dietary sodium restriction) 1

Urine Osmolality >100 mOsm/kg with Urine Sodium <30 mmol/L: 1, 2

• Hypovolemic causes: GI losses, diuretics (remote use), burns, third-spacing
• Hypervolemic causes: Heart failure, cirrhosis, nephrotic syndrome
• Urine sodium <30 mmol/L has 71-100% positive predictive value for response to 0.9% saline 1

Urine Osmolality >100 mOsm/kg with Urine Sodium >40 mmol/L: 1, 2

• SIADH (euvolemic, urine osm >500 mOsm/kg, normal thyroid/adrenal function)
• Cerebral salt wasting (hypovolemic, neurosurgical patients)
• Diuretic use (active)
• Adrenal insufficiency or hypothyroidism

Treatment Based on Symptom Severity

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

This is a medical emergency requiring immediate intervention: 1, 3, 4

• Administer 3% hypertonic saline as 100 mL bolus over 10 minutes 1
• Can repeat up to 3 times at 10-minute intervals until symptoms resolve 1
• Target correction: 4-6 mmol/L over first 6 hours or until symptoms abate 1, 3
• Maximum correction limit: 8 mmol/L in 24 hours 1, 3, 4
• Monitor serum sodium every 2 hours during active correction 1
• Consider ICU admission for close monitoring 1

Critical safety point: Even in symptomatic patients, do not exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 1, 3, 4

Asymptomatic or Mildly Symptomatic Hyponatremia

Treatment depends on volume status and underlying etiology:

Hypovolemic Hyponatremia

• Discontinue diuretics immediately 1
• Administer isotonic (0.9%) saline for volume repletion 1
• Target correction rate: 4-8 mmol/L per day, not exceeding 8 mmol/L in 24 hours 1
• Monitor sodium every 4 hours initially 1

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 3
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1
• For resistant cases, consider: 1, 3
  • Urea (40g in 100-150 mL normal saline every 8 hours for neurosurgical patients) 1
  • Loop diuretics
  • Demeclocycline or lithium (less commonly used due to side effects)
  • Vaptans (tolvaptan 15 mg daily, titrate based on response) 1, 5

Hypervolemic Hyponatremia (Heart Failure, Cirrhosis)

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1, 3
• Sodium restriction (2-2.5 g/day or 88-110 mmol/day) 1
• Discontinue diuretics temporarily if sodium <125 mmol/L 1
• For cirrhosis: Consider albumin infusion (6-8 g per liter of ascites drained) 1
• Avoid hypertonic saline unless life-threatening symptoms present (worsens edema/ascites) 1
• Vaptans may be considered for persistent severe hyponatremia despite fluid restriction, but use with extreme caution in cirrhosis due to 10% risk of GI bleeding vs 2% with placebo 1, 5

Special Populations and Critical Distinctions

Neurosurgical Patients: SIADH vs Cerebral Salt Wasting (CSW)

This distinction is critical as treatments are opposite: 1, 2

SIADH characteristics:

• Euvolemic on exam
• Urine sodium >40 mmol/L
• Urine osmolality >500 mOsm/kg
• Treatment: Fluid restriction to 1 L/day 1

CSW characteristics:

• Hypovolemic on exam (hypotension, tachycardia, dry mucous membranes)
• Urine sodium >40 mmol/L
• More common in poor clinical grade SAH, anterior communicating artery aneurysms 1
• Treatment: Volume and sodium replacement with isotonic or hypertonic saline 1
• For severe symptoms: 3% hypertonic saline + fludrocortisone in ICU 1
• Never use fluid restriction in CSW (worsens outcomes and increases vasospasm risk) 1

High-Risk Patients for Osmotic Demyelination Syndrome

Use more cautious correction rates (4-6 mmol/L per day, maximum 8 mmol/L in 24 hours) in: 1, 3

• Advanced liver disease or cirrhosis
• Alcoholism
• Malnutrition
• Severe hyponatremia (<120 mmol/L)
• Hypokalemia, hypophosphatemia
• Prior encephalopathy

Cirrhotic Patients

Hyponatremia in cirrhosis carries significant prognostic implications: 1

• Sodium ≤130 mmol/L increases risk of:
  • Spontaneous bacterial peritonitis (OR 3.40)
  • Hepatorenal syndrome (OR 3.45)
  • Hepatic encephalopathy (OR 2.36)
• Hyponatremia is mostly hypervolemic and dilutional 1
• It is sodium restriction, not fluid restriction, that results in weight loss (fluid follows sodium) 1
• Albumin infusion should be tried before vaptans 1
• Tolvaptan carries higher risk of GI bleeding (10% vs 2% placebo) and increased all-cause mortality with long-term use 1, 5

Management of Overcorrection

If sodium correction exceeds 8 mmol/L in 24 hours: 1

• Immediately discontinue current fluids
• Switch to D5W (5% dextrose in water) to relower sodium
• Consider administering desmopressin to slow or reverse rapid rise
• Target: Bring total 24-hour correction to ≤8 mmol/L from starting point
• Monitor for osmotic demyelination syndrome signs (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1

Common Pitfalls to Avoid

• Ignoring mild hyponatremia (130-135 mmol/L): Associated with increased falls (21% vs 5%), fractures, cognitive impairment, and 60-fold increase in mortality when <130 mmol/L 1, 3
• Using fluid restriction in cerebral salt wasting: Worsens outcomes and increases vasospasm risk 1
• Overly rapid correction in chronic hyponatremia: Leads to osmotic demyelination syndrome 1, 3, 4
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms: Worsens edema and ascites 1
• Inadequate monitoring during active correction: Check sodium every 2 hours during severe symptomatic treatment, every 4 hours after symptom resolution 1
• Failing to distinguish SIADH from CSW in neurosurgical patients: Leads to opposite and potentially harmful treatment 1, 2
• Misdiagnosing volume status in heart failure patients: Can lead to inappropriate treatment 1, 2

Monitoring Parameters

During active correction: 1

• Serum sodium every 2 hours for severe symptoms
• Serum sodium every 4 hours after symptom resolution
• Daily weights and fluid balance
• Watch for neurological changes suggesting overcorrection

Chronic management: 1

• Daily sodium monitoring until stable
• Assess for underlying cause resolution
• Monitor for complications of underlying disease