Workup of Hyponatremia
Begin with serum sodium <135 mmol/L as the threshold for hyponatremia, but pursue a comprehensive workup when sodium drops below 131 mmol/L. 1
Initial Laboratory Assessment
Obtain the following tests immediately to determine the underlying cause: 1
- Serum osmolality (normal: 275-290 mOsm/kg) to exclude pseudohyponatremia from hyperglycemia, hypertriglyceridemia, or laboratory error 1, 2
- Urine osmolality to assess water excretion capacity (>100 mOsm/kg suggests impaired water excretion) 1, 2
- Urine sodium concentration to differentiate renal from extrarenal causes 1, 2
- Serum uric acid (<4 mg/dL has 73-100% positive predictive value for SIADH) 1, 2
- Thyroid-stimulating hormone (TSH) to rule out hypothyroidism 1
- Serum creatinine and blood urea nitrogen to assess renal function 1
Volume Status Assessment
Determine extracellular fluid volume status through physical examination, though recognize this has limited accuracy (sensitivity 41.1%, specificity 80%). 1, 2
Hypovolemic Signs
- Orthostatic hypotension (drop in systolic BP >20 mmHg or diastolic >10 mmHg upon standing) 1, 2
- Dry mucous membranes and decreased skin turgor 1, 2
- Flat neck veins 2
- Tachycardia 1
Euvolemic Signs
Hypervolemic Signs
Diagnostic Algorithm Based on Urine Studies
If Urine Sodium <30 mmol/L
- Hypovolemic hyponatremia from extrarenal losses (GI losses, burns, dehydration) with 71-100% positive predictive value for response to 0.9% saline 1, 2
- Consider third-space losses 1
If Urine Sodium >20-40 mmol/L with Urine Osmolality >300 mOsm/kg
- Euvolemic: SIADH (malignancy, CNS disorders, pulmonary disease, medications) 1, 2
- Hypovolemic: Cerebral salt wasting (CSW), diuretic use, adrenal insufficiency, salt-losing nephropathy 2
- Hypervolemic: Advanced renal failure 2
If Urine Osmolality <100 mOsm/kg
- Primary polydipsia or appropriate ADH suppression 2
Special Considerations for Neurosurgical Patients
In patients with CNS pathology (subarachnoid hemorrhage, brain injury, post-neurosurgery), distinguishing SIADH from cerebral salt wasting is critical as they require opposite treatments. 1, 2
SIADH Characteristics
- Euvolemic state (normal to slightly elevated CVP 6-10 cm H₂O) 2
- Urine sodium >20-40 mmol/L 2
- Urine osmolality >500 mOsm/kg 2
- Treatment: Fluid restriction 1, 2
Cerebral Salt Wasting Characteristics
- True hypovolemia (CVP <6 cm H₂O) 2
- Urine sodium >20 mmol/L despite volume depletion 2
- Clinical signs of hypovolemia (hypotension, tachycardia, dry mucous membranes) 1
- Treatment: Volume and sodium replacement, NOT fluid restriction 1, 2
Tests NOT Recommended
Do not obtain ADH or natriuretic peptide levels, as these are not supported by evidence and should not delay treatment. 1, 2
Classification by Volume Status
Hypovolemic Hyponatremia
- Urine sodium <30 mmol/L: GI losses, burns, third-spacing 1, 2
- Urine sodium >20 mmol/L: Diuretics, CSW, adrenal insufficiency, salt-losing nephropathy 1, 2
Euvolemic Hyponatremia
- SIADH (most common): Malignancy, CNS disorders, pulmonary disease, medications (SSRIs, carbamazepine, cyclophosphamide) 1, 2
- Hypothyroidism, adrenal insufficiency (check TSH, cortisol) 1
- Primary polydipsia (urine osmolality <100 mOsm/kg) 2
Hypervolemic Hyponatremia
- Heart failure: Elevated BNP, peripheral edema, JVD 1
- Cirrhosis: Ascites, elevated liver enzymes, low albumin 1
- Renal failure: Elevated creatinine, urine sodium >20 mmol/L 2
Common Pitfalls to Avoid
- Relying solely on physical examination for volume status determination (sensitivity only 41.1%) 1, 2
- Failing to distinguish SIADH from CSW in neurosurgical patients, leading to inappropriate fluid restriction in CSW which worsens outcomes 1, 2
- Obtaining ADH levels, which delays treatment without providing actionable information 1, 2
- Ignoring mild hyponatremia (130-135 mmol/L), which increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1