Hyponatremia: Laboratory Evaluation and Treatment
Laboratory Tests Required for Initial Workup
The essential laboratory evaluation for hyponatremia includes serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and clinical assessment of extracellular fluid volume status. 1
Core Laboratory Panel
- Serum osmolality to exclude pseudohyponatremia (normal: 275-290 mOsm/kg) 1
- Urine osmolality to assess water excretion capacity: <100 mOsm/kg indicates appropriate ADH suppression, while >100 mOsm/kg suggests impaired water excretion 1
- Urine sodium concentration to differentiate causes: <30 mmol/L suggests extrarenal losses (71-100% positive predictive value for saline responsiveness), while >20-40 mmol/L suggests renal losses or SIADH 1, 2
- Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2
- Serum creatinine and BUN to assess renal function and volume status 1
Additional Tests Based on Clinical Context
- Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
- Cortisol level if adrenal insufficiency is suspected 1
- Serum glucose to exclude hyperglycemia-induced pseudohyponatremia (adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL) 1
- Liver function tests and albumin in patients with suspected cirrhosis 1
Tests NOT Recommended
Do not routinely order plasma ADH levels or natriuretic peptide levels—these are not supported by evidence and delay diagnosis. 1, 3
Treatment Approach Based on Symptom Severity and Volume Status
Step 1: Assess Symptom Severity
Severe symptomatic hyponatremia (seizures, coma, altered consciousness, respiratory distress) is a medical emergency requiring immediate hypertonic saline. 1, 3
- Administer 3% hypertonic saline as 100-150 mL IV bolus over 10 minutes, repeatable up to 3 times at 10-minute intervals 1
- Target correction: 6 mmol/L over first 6 hours or until symptoms resolve 1
- Monitor serum sodium every 2 hours during initial correction 1
Mild to moderate symptoms (nausea, headache, confusion, weakness) require slower correction with close monitoring. 3
Step 2: Determine Volume Status
Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%), so combine clinical findings with laboratory data. 1
Hypovolemic Hyponatremia (orthostatic hypotension, dry mucous membranes, decreased skin turgor)
- 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
- Urine sodium <30 mmol/L predicts good response to saline (71-100% positive predictive value) 1
Euvolemic Hyponatremia (SIADH) (no edema, normal volume status)
- Fluid restriction to 1 L/day is first-line 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 1
- Diagnostic criteria: urine osmolality >300 mOsm/kg, urine sodium >20-40 mEq/L, serum uric acid <4 mg/dL, normal thyroid/adrenal function 2
Hypervolemic Hyponatremia (peripheral edema, ascites, jugular venous distention)
- Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1
- Discontinue diuretics temporarily until sodium improves 1
- Consider albumin infusion in cirrhotic patients (8 g per liter of ascites removed) 1
- Avoid hypertonic saline unless life-threatening symptoms present—it worsens edema and ascites 1
Critical Correction Rate Guidelines
The maximum correction rate is 8 mmol/L in any 24-hour period to prevent osmotic demyelination syndrome. 1, 4, 5
Standard-Risk Patients
- Target 4-8 mmol/L per day, not exceeding 10-12 mmol/L in 24 hours 1
High-Risk Patients (cirrhosis, alcoholism, malnutrition, prior encephalopathy)
- Limit to 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1
- Risk of osmotic demyelination syndrome is 0.5-1.5% even with careful correction 1
Management of Overcorrection
If sodium rises >8 mmol/L in 24 hours, immediately stop hypertonic saline and administer D5W (5% dextrose in water) or desmopressin to relower sodium. 1
Special Populations
Neurosurgical Patients: Distinguishing SIADH from Cerebral Salt Wasting (CSW)
This distinction is critical because treatments are opposite—SIADH requires fluid restriction while CSW requires volume expansion. 1, 2
- SIADH: Euvolemic, CVP 6-10 cm H₂O, treat with fluid restriction 1
- CSW: Hypovolemic, CVP <6 cm H₂O, urine sodium >20 mmol/L despite volume depletion, treat with isotonic/hypertonic saline and fludrocortisone 0.1-0.2 mg daily 1
- Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm—it worsens outcomes 1
Cirrhotic Patients
- Hyponatremia increases risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
- Require more cautious correction (4-6 mmol/L per day) due to higher osmotic demyelination risk 1
- Sodium restriction (2-2.5 g/day), not fluid restriction, results in weight loss as fluid follows sodium 1
Common Pitfalls to Avoid
- Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours—this causes osmotic demyelination syndrome (dysarthria, dysphagia, quadriparesis appearing 2-7 days post-correction) 1
- Never use fluid restriction in cerebral salt wasting—it worsens outcomes and can precipitate cerebral ischemia 1
- Never ignore mild hyponatremia (130-135 mmol/L)—it increases fall risk (21% vs 5%), fractures, and mortality (60-fold increase with sodium <130 mmol/L) 1, 3
- Never rely solely on physical examination for volume status—combine with urine sodium, osmolality, and laboratory trends 1
- Never use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms—it exacerbates fluid overload 1