What are the causes of hyponatremia, its diagnostic workup, and treatment options?

Causes, Diagnostic Workup, and Treatment of Hyponatremia

Hyponatremia should be evaluated based on volume status and serum osmolality, with treatment tailored to the underlying cause and symptom severity while maintaining a maximum correction rate of 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 1

Causes of Hyponatremia

Hyponatremia (serum sodium <135 mmol/L) can be classified based on volume status and osmolality:

Based on Volume Status:

• Hypovolemic hyponatremia: Caused by sodium and fluid loss from:

  • Excessive diuretic use (especially thiazides) 1, 2
  • Gastrointestinal losses (vomiting, diarrhea) 2, 3
  • Significant blood loss 3
  • Burns 1

• Euvolemic hyponatremia:

  • Syndrome of Inappropriate ADH secretion (SIADH) 1, 2
  • Medications (antidepressants, antipsychotics, anticonvulsants) 2, 4
  • Endocrine disorders (hypothyroidism, adrenal insufficiency) 1
  • Reset osmostat syndrome 1
  • Excessive water intake 2, 4
  • Beer potomania 1

• Hypervolemic hyponatremia:

  • Congestive heart failure 1, 2
  • Liver cirrhosis 1, 2
  • Renal disease 2
  • Nephrotic syndrome 3

Based on Osmolality:

• Hypotonic hyponatremia: Most common form 5
• Isotonic hyponatremia: Pseudohyponatremia 2
• Hypertonic hyponatremia: Caused by hyperglycemia 2

Diagnostic Workup

Initial Assessment:

1. History and physical examination to assess volume status:

   • Hypovolemia: Orthostatic hypotension, dry mucous membranes, decreased skin turgor 1
   • Euvolemia: Normal skin turgor, moist mucous membranes, no edema 1
   • Hypervolemia: Edema, ascites, distended jugular veins, pulmonary rales 3

2. Laboratory evaluation:

   • Serum sodium, potassium, chloride, bicarbonate 1
   • Serum osmolality 1
   • Urine osmolality and electrolytes 1
   • Serum uric acid (levels <4 mg/dL have 73-100% positive predictive value for SIADH) 1
   • Thyroid function tests and cortisol level to rule out endocrine causes 1
   • Liver function tests and albumin if liver disease suspected 1
   • Complete blood count 1
   • Renal function tests (BUN, creatinine) 1

3. Interpretation of laboratory results:

   • Urine sodium <30 mmol/L with low plasma osmolality suggests hypovolemic hyponatremia (71-100% predictive value for response to saline) 1
   • Urine sodium >20 mmol/L with high urine osmolality (>500 mOsm/kg) suggests SIADH 1
   • Low urine osmolality (<100 mOsm/kg) with low urine sodium suggests hypovolemic hyponatremia 1

Treatment of Hyponatremia

General Principles:

• Treatment should be based on:
  • Symptom severity (mild vs. severe)
  • Acuity of onset (acute <48 hours vs. chronic >48 hours)
  • Volume status (hypovolemic, euvolemic, hypervolemic) 1
• Maximum correction rate: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1
• For high-risk patients (liver disease, alcoholism, malnutrition): 4-6 mmol/L per day 1

Treatment Based on Symptom Severity:

Severe Symptomatic Hyponatremia (seizures, coma):

• Administer 3% hypertonic saline with goal to correct 6 mmol/L over 6 hours or until symptoms resolve 1
• Can be given as boluses of 100 mL over 10 minutes, repeated up to three times at 10-minute intervals until symptoms improve 1
• Consider ICU admission for close monitoring 1
• Monitor serum sodium every 2 hours during initial correction 1

Mild/Asymptomatic Hyponatremia:

• Treatment based on volume status (see below) 1
• Monitor serum sodium levels regularly 1

Treatment Based on Volume Status:

Hypovolemic Hyponatremia:

• Discontinue diuretics 1
• Administer isotonic saline (0.9% NaCl) for volume repletion 1, 3
• For severe dehydration with neurological symptoms, consider hypertonic saline with careful monitoring 1

Euvolemic Hyponatremia (SIADH):

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 5
• For resistant cases, consider:
  • Oral sodium chloride (100 mEq three times daily) 1
  • Urea 1
  • Vasopressin receptor antagonists (tolvaptan) for euvolemic or hypervolemic hyponatremia 1, 6
  • Demeclocycline, lithium (less commonly used due to side effects) 1, 2

Hypervolemic Hyponatremia:

• Fluid restriction to 1-1.5 L/day for serum sodium <125 mmol/L 1
• Sodium restriction (80-120 mmol/day) 1
• For cirrhosis: Consider albumin infusion 1
• For heart failure: Optimize heart failure therapy 1
• Avoid hypertonic saline unless life-threatening symptoms are present 1

Special Considerations:

Cerebral Salt Wasting vs. SIADH in Neurosurgical Patients:

• CSW requires volume and sodium replacement, not fluid restriction 1
• Consider fludrocortisone for hyponatremia in subarachnoid hemorrhage patients 1
• Avoid fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1

Overcorrection Management:

• If overcorrection occurs, consider relowering with electrolyte-free water or desmopressin 1
• Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1

Common Pitfalls to Avoid

• Overly rapid correction of chronic hyponatremia leading to osmotic demyelination syndrome 1
• Inadequate monitoring during active correction 1
• Using fluid restriction in cerebral salt wasting (can worsen 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 (135 mmol/L) as clinically insignificant 1
• Misdiagnosing volume status, particularly distinguishing between SIADH and cerebral salt wasting 1, 7