Hyponatremia

Etiologies

• Medications: thiazide and thiazide-type diuretics, mannitol, IVIG, desmopressin (dDAVP), ecstasy (methylenedioxymethamphetamine), and some antidepressants, antiepileptics, and antipsychotics

Differential Diagnosis

• Pseudohyponatremia from lab error
• Translational hyponatremia from mannitol or hyperglycemia
• Hypovolemic
  • U_Na >20: Renal losses, including mineralocorticoid deficiency
  • U_Na <10: Non-renal losses
• Euvolemic
  • U_osm >100: SIADH, hypothyroidism, glucocorticoid deficiency
  • U_osm <100: Primary polydipsia, low solute intake
  • U_osm variable: Reset osmostat
• Hypervolemic
  • U_Na <10: CHD, cirrhosis, nephrosis
  • U_Na >20: Renal failure

Investigations

• Serum and urine osmolality and electrolytes (prior to treatment)
• TSH and AM cortisol

Diagnosis by Lab Criteria

• Serum Na (S_Na) <134?
• Measure serum osmolality (S_osm) and urea level (S_urea)
  • S_osm ≥ 280: normotonic/hypertonic
    • Differential includes pseudohyponatremia (from hyperlipidemia, hyperparaproteinemia, etc.), or presence of osmotically active substances (glucose, mannitol)
  • S_osm <280 mOsm/kg: true hyponatremia
    • Measure urine osmolality (U_osm)
    • U_osm <100 mOsm/kg: normal water excretion
      • Primary polydipsia or reset osmostat syndrome
    • U_osm ≥ 100 mOsm/kg: impaired water excretion
      • Exclude hypothyroidism and adrenal insufficiency with morning cortisol and TSH
      • Measure urine sodium (U_Na)
      • U_Na < 20 mmol/L: hypovolemia, including EABV depletion (heart failure, cirrhosis, nephrotic syndrome)
      • U_Na > 40 mmol/L: SIADH, reset osmostat, renal salt wasting
        • Salt supplementation and water restriction
        • Normal S_urate and reduced FE_urate: SIADH
        • Hypouricemia and unchanged FE_urate: renal salt wasting
      • U_Na between 20 and 40 mmol/L
        • Bolus 2 L/day normal saline for 2 days and trend sodium
        • If S_Na increases by ≥ 5 mmol/L: hypovolemia
        • If S_Na increases by <5 mmol/L: SIADH or reset osmostat
          • FE_urea >55%, S_urate <0.24, and FE_urate >10%: SIADH
          • Oral or IV water-loading test: reset osmostat

Management

• Depends on cause
  • Hypovolemic: fluid resuscitation
  • Euvolemic: fluid restriction
  • Hypervolemic: fluid restriction and/or diuretics
• Goal rate of correction in chronic hyponatremia should be 4 to 6 mEq/L in 24 hours (max of 8 mEq) in order to reduce the risk of osmotic demyelination syndrome
• For patients with hyponatremia (less than 125) with severe symptoms (coma, seizure, respiratory distress) or moderately severe symptoms with risk of (confusion or vomiting) who are at risk of progression, consider hypertonic saline 3% 100-150 mL IV bolus over 10-20 minutes
  • Trend sodium closely
  • Not indicated for asymptomatic or mildly symptomatic chronic hyponatremia

Further Reading

• Milionis HJ, Liamis GL, and Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. 2002;166(8):1056-1062.