What is the recommended workup and treatment approach for a patient with hyponatremia by a nephrologist?

Hyponatremia Workup by a Nephrologist

The initial workup should include serum and urine osmolality, urine sodium, urine electrolytes, serum uric acid, and clinical assessment of extracellular fluid volume status to determine the underlying cause, with treatment guided by volume status (hypovolemic, euvolemic, or hypervolemic) and symptom severity. 1

Initial Diagnostic Workup

Essential Laboratory Tests

• Serum osmolality to exclude pseudohyponatremia (normal: 275-290 mOsm/kg) 1
• Urine osmolality and urine sodium concentration to determine water excretion capacity and differentiate causes 1, 2
• Serum uric acid <4 mg/dL has a 73-100% positive predictive value for SIADH 1, 2
• Serum creatinine, electrolytes (including potassium, calcium, magnesium) to rule out other causes 1
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1

Volume Status Assessment

Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for determining volume status 1, 2. Look for:

• Hypovolemic signs: orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1, 2
• Hypervolemic signs: peripheral edema, ascites, jugular venous distention, pulmonary congestion 1, 2
• Euvolemic: absence of both hypovolemic and hypervolemic signs 2

Urine Studies Interpretation

• Urine sodium <30 mmol/L suggests hypovolemic hyponatremia with 71-100% positive predictive value for saline responsiveness 1, 2
• Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg supports SIADH in euvolemic patients 1, 2
• **Urine osmolality <100 mOsm/kg** indicates appropriate ADH suppression, while >100 mOsm/kg suggests impaired water excretion 1

Tests NOT Recommended

Do not routinely order plasma ADH levels or natriuretic peptide levels, as these are not supported by evidence and delay diagnosis 1, 2

Treatment Algorithm Based on Volume Status

Hypovolemic Hyponatremia

• Discontinue diuretics immediately if sodium <125 mmol/L 1
• Administer isotonic saline (0.9% NaCl) for volume repletion at 15-20 mL/kg/h initially, then 4-14 mL/kg/h based on response 1
• Common causes: gastrointestinal losses, diuretic use, cerebral salt wasting, adrenal insufficiency 1, 2

Euvolemic Hyponatremia (SIADH)

• Fluid restriction to 1 L/day is the cornerstone of treatment 1, 2
• Add oral sodium chloride 100 mEq three times daily if no response to fluid restriction 1
• Consider vasopressin receptor antagonists (tolvaptan 15 mg once daily) for resistant cases, titrating to 30-60 mg 1, 3
• Diagnostic criteria: hypotonic hyponatremia, urine osmolality >500 mOsm/kg, urine sodium >20-40 mEq/L, euvolemia, normal thyroid/adrenal function 2

Hypervolemic Hyponatremia

• Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1
• Discontinue diuretics temporarily until sodium improves 1
• For cirrhosis: consider albumin infusion alongside fluid restriction 1
• Avoid hypertonic saline unless life-threatening symptoms present, as it worsens ascites and edema 1
• Common causes: heart failure, cirrhosis, renal disease 1, 4

Treatment Based on Symptom Severity

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

• Administer 3% hypertonic saline immediately with target correction of 6 mmol/L over 6 hours or until symptoms resolve 1, 5, 6
• Monitor serum sodium every 2 hours during initial correction 1
• This is a medical emergency requiring ICU admission 1

Mild to Moderate Symptoms

• Treat based on volume status as outlined above 1
• Monitor serum sodium every 24-48 hours initially 1

Critical Correction Rate Guidelines

The maximum correction rate must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 3, 5. This is the single most important safety principle.

High-Risk Patients Requiring Slower Correction (4-6 mmol/L per day)

• Advanced liver disease 1
• Alcoholism 1
• Malnutrition 1, 3
• Severe hyponatremia (<120 mmol/L) 1

If Overcorrection Occurs

• Immediately discontinue current fluids and switch to D5W 1
• Consider administering desmopressin to slow or reverse the rapid rise 1

Special Considerations in Neurosurgical Patients

Distinguish between SIADH and cerebral salt wasting (CSW), as they require opposite treatments 1, 2:

• SIADH: euvolemic, CVP 6-10 cm H₂O, treat with fluid restriction 1, 2
• CSW: hypovolemic, CVP <6 cm H₂O, treat with volume and sodium replacement (NOT fluid restriction) 1, 2
• For CSW with severe symptoms: use 3% hypertonic saline plus fludrocortisone 0.1-0.2 mg daily 1
• In subarachnoid hemorrhage patients at risk of vasospasm: never use fluid restriction 1

Common Pitfalls to Avoid

• Overly rapid correction exceeding 8 mmol/L in 24 hours causes osmotic demyelination syndrome 1, 3
• Using fluid restriction in cerebral salt wasting worsens outcomes 1
• Inadequate monitoring during active correction 1
• Failing to recognize and treat the underlying cause 1
• Using hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant, especially in high-risk populations 1, 5