How to evaluate and manage a patient with hyponatremia, considering their volume status, underlying medical conditions, and symptoms?

Evaluation of Hyponatremia

Initial Diagnostic Workup

Begin by confirming true hypotonic hyponatremia through serum osmolality (<275 mOsm/kg) and exclude pseudohyponatremia from hyperglycemia by correcting sodium (add 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL). 1

Essential Laboratory Tests

• Serum osmolality to confirm hypotonic hyponatremia (normal: 275-290 mOsm/kg) 2
• Urine osmolality to assess water excretion capacity (>100 mOsm/kg suggests impaired water excretion) 2
• Urine sodium concentration to differentiate causes:
  • <30 mmol/L suggests extrarenal losses (hypovolemic) with 71-100% positive predictive value for saline responsiveness 2, 3

  • 20-40 mmol/L suggests renal losses, SIADH, or cerebral salt wasting 2, 3

• Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 2, 3
• Serum creatinine, thyroid function (TSH), and cortisol to exclude endocrine causes 1

Volume Status Assessment

Physical examination alone is unreliable for determining volume status (sensitivity 41.1%, specificity 80%), so combine clinical findings with laboratory data. 2, 3

Hypovolemic signs:

• Orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 2

Euvolemic signs:

• No edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 2

Hypervolemic signs:

• Peripheral edema, ascites, jugular venous distention, pulmonary congestion 2

Diagnostic Algorithm by Volume Status

Hypovolemic Hyponatremia

• Urine sodium <30 mmol/L: Extrarenal losses (GI losses, burns, dehydration) 2
• Urine sodium >20 mmol/L: Renal losses (diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy) 2, 3

Euvolemic Hyponatremia

• Urine sodium >20-40 mmol/L + urine osmolality >300 mOsm/kg: SIADH 2, 3
• Common causes: Malignancies (especially small cell lung cancer), CNS disorders, pulmonary diseases, medications (SSRIs, carbamazepine, cyclophosphamide) 2
• Rule out: Hypothyroidism, adrenal insufficiency, polydipsia 2

Hypervolemic Hyponatremia

• Urine sodium >20 mmol/L: Advanced renal failure 3
• Urine sodium variable: Heart failure, cirrhosis 2

Special Considerations in Neurosurgical Patients

Distinguishing SIADH from cerebral salt wasting (CSW) is critical as they require opposite treatments. 2, 3

SIADH characteristics:

• Euvolemic state, normal to slightly elevated CVP (6-10 cm H₂O) 2
• Urine sodium >20-40 mmol/L, urine osmolality >500 mOsm/kg 3
• Treatment: Fluid restriction 2

CSW characteristics:

• True hypovolemia, CVP <6 cm H₂O 2
• Urine sodium >20 mmol/L despite volume depletion 2
• Evidence of extracellular volume depletion (hypotension, tachycardia, dry mucous membranes) 2
• Treatment: Volume and sodium replacement, NOT fluid restriction 2

Tests NOT Recommended

Do not routinely order plasma ADH levels or natriuretic peptide levels—these are not supported by evidence and delay diagnosis. 2, 3

Symptom Assessment for Treatment Planning

Categorize by symptom severity:

• Severe symptoms (medical emergency): Seizures, coma, somnolence, obtundation, cardiorespiratory distress 4
• Moderate symptoms: Confusion, nausea, vomiting, headache 5
• Mild symptoms: Weakness, mild neurocognitive deficits 5
• Asymptomatic: No symptoms but sodium <135 mEq/L 2

Even mild chronic hyponatremia (130-135 mEq/L) is clinically significant—it increases fall risk (21% vs 5% in normonatremic patients) and mortality (60-fold increase with sodium <130 mmol/L). 2

Common Diagnostic Pitfalls to Avoid

• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant 2
• Relying solely on physical examination to determine volume status 2
• Failing to distinguish SIADH from CSW in neurosurgical patients 2, 3
• Delaying treatment while pursuing diagnostic workup in symptomatic patients 5
• Misdiagnosing volume status in heart failure patients with hyponatremia 2