What are the causes and treatment options for hyponatremia?

Causes of Hyponatremia

Hyponatremia is the most common electrolyte abnormality in hospitalized patients, occurring in 15-30% of cases, and can be classified based on volume status as hypovolemic, euvolemic, or hypervolemic, each with distinct causes requiring different management approaches. 1

Classification by Volume Status

Hypovolemic Hyponatremia

• Clinical signs: Orthostatic hypotension, dry mucous membranes, tachycardia
• Urine sodium: <20 mEq/L
• Common causes:
  • Gastrointestinal losses (vomiting, diarrhea)
  • Diuretic use (especially thiazides)
  • Cerebral salt wasting (CSW)
  • Adrenal insufficiency
  • Severe burns
  • Third-space losses

Euvolemic Hyponatremia

• Clinical signs: No edema, normal vital signs
• Urine sodium: >20-40 mEq/L
• Common causes:
  • Syndrome of Inappropriate ADH secretion (SIADH)
  • Hypothyroidism
  • Adrenal insufficiency
  • Reset osmostat syndrome
  • Medications (antidepressants, antipsychotics, anticonvulsants)
  • Excessive water intake (psychogenic polydipsia)
  • Post-operative state

Hypervolemic Hyponatremia

• Clinical signs: Edema, ascites, elevated JVP
• Urine sodium: <20 mEq/L
• Common causes:
  • Heart failure
  • Liver cirrhosis
  • Renal failure
  • Nephrotic syndrome

Medication-Induced Hyponatremia

Medications are a significant cause of hyponatremia, particularly:

• Thiazide diuretics: Risk factors include age, female sex, and low body mass 2
• Antidepressants (SSRIs, SNRIs)
• Antipsychotics
• Anticonvulsants (carbamazepine, oxcarbazepine)
• NSAIDs
• ACE inhibitors

Severity Classification

Hyponatremia can be categorized by severity 3:

• Mild: 130-135 mEq/L
• Moderate: 125-129 mEq/L
• Severe: <125 mEq/L

Clinical Manifestations

The symptoms depend on the severity and rate of development:

• Mild symptoms: Nausea, vomiting, headache, weakness, mild neurocognitive deficits
• Severe symptoms: Delirium, confusion, impaired consciousness, ataxia, seizures, and rarely brain herniation and death 3

Special Considerations

Cirrhosis

Patients with liver cirrhosis and hyponatremia have:

• Poorer prognosis
• Higher risk of refractory ascites
• Increased risk of spontaneous bacterial peritonitis
• Higher risk of hepatorenal syndrome 1

Elderly Patients

• More susceptible to medication-induced hyponatremia
• Higher risk of complications from hyponatremia
• Even mild hyponatremia associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 4

Diagnostic Approach

1. Confirm true hyponatremia by checking plasma osmolality:

   • High plasma osmolality: Consider hyperglycemia
   • Normal plasma osmolality: Consider pseudohyponatremia or post-TURP syndrome
   • Low plasma osmolality: True hyponatremia 5

2. Assess volume status to categorize as hypovolemic, euvolemic, or hypervolemic

3. Check urine sodium to further narrow differential diagnosis:

   • <20 mEq/L: Suggests extrarenal sodium loss or effective circulating volume depletion

   • 20 mEq/L: Suggests renal sodium loss or SIADH 1

Treatment Considerations

Treatment should be guided by:

1. Severity of symptoms
2. Duration of hyponatremia (acute vs. chronic)
3. Volume status

For severe symptomatic hyponatremia, 3% hypertonic saline is recommended with careful monitoring to prevent overly rapid correction and risk of osmotic demyelination syndrome 1, 6.

For chronic hyponatremia, the recommended correction rate is 4-6 mEq/L per 24-hour period, not exceeding 8 mEq/L per 24 hours 1.

For SIADH or hypervolemic hyponatremia, tolvaptan (a vasopressin receptor antagonist) may be considered for short-term treatment (≤30 days) 7.

Pitfalls to Avoid

• Overly rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome
• Underestimation of mild hyponatremia, which is associated with cognitive impairment and increased fall risk
• Failure to identify the underlying cause, which is essential for effective management
• Inappropriate fluid management (e.g., using hypotonic fluids in hyponatremia)
• Inadequate monitoring during correction of severe hyponatremia

Remember that even mild hyponatremia is associated with increased hospital stay and mortality, making prompt identification and appropriate management crucial 4.