Hyponatremia Workup
Initial Diagnostic Evaluation
Begin with serum sodium <135 mEq/L as the threshold for hyponatremia, but pursue a comprehensive workup when sodium drops below 131 mEq/L 1.
Essential Laboratory Tests
- Serum osmolality to exclude pseudohyponatremia (normal: 275-290 mOsm/kg) 1, 2
- Urine osmolality and urine sodium concentration to determine water excretion capacity and differentiate causes 1, 2
- Serum and urine electrolytes including potassium, calcium, and magnesium 1
- Serum uric acid – levels <4 mg/dL have a 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
- Serum glucose – hyperglycemia causes pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 1
Tests NOT Recommended
Do not routinely order plasma ADH levels or natriuretic peptide levels – these are not supported by evidence (class III) and delay diagnosis 1, 2.
Volume Status Assessment
Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for determining volume status 1, 2. However, assess for the following:
Hypovolemic Signs
- Orthostatic hypotension, dry mucous membranes, decreased skin turgor, flat neck veins 1
- Urine sodium <30 mmol/L has a 71-100% positive predictive value for response to 0.9% saline infusion 1, 2
Euvolemic Signs
- Normal volume status: no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes 1
- Urine sodium >20-40 mmol/L with urine osmolality >300 mOsm/kg suggests SIADH 1, 2
Hypervolemic Signs
- Peripheral edema, ascites, jugular venous distention, pulmonary congestion 1
- Urine sodium >20 mmol/L due to compensatory natriuresis 1
Diagnostic Algorithm by Volume Status
Hypovolemic Hyponatremia
- Urine sodium <30 mmol/L: extrarenal losses (GI losses, burns, dehydration) 1, 2
- Urine sodium >20 mmol/L: renal losses (diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy) 1, 2
Euvolemic Hyponatremia
- Urine osmolality <100 mOsm/kg: appropriate ADH suppression (primary polydipsia) 1
- Urine osmolality >100 mOsm/kg with urine sodium >20-40 mEq/L: SIADH 1, 2
- Rule out hypothyroidism, hypocortisolism, and medications (SSRIs, carbamazepine, NSAIDs, opioids, chemotherapy) 1, 2
Hypervolemic Hyponatremia
- Urine sodium >20 mmol/L: advanced renal failure 2
- Urine sodium variable: heart failure, cirrhosis 1
- Check liver function tests for cirrhosis and BNP for heart failure 1
Special Considerations in Neurosurgical Patients
Distinguishing between SIADH and cerebral salt wasting (CSW) is critical, as they require opposite treatments 1, 2:
SIADH Characteristics
- Euvolemic state (CVP 6-10 cm H₂O) 1
- Urine sodium >20-40 mEq/L 1, 2
- Urine osmolality >500 mOsm/kg 2
- Treatment: fluid restriction 1, 2
Cerebral Salt Wasting Characteristics
- True hypovolemia (CVP <6 cm H₂O) 1
- Urine sodium >20 mmol/L despite volume depletion 1, 2
- Evidence of extracellular volume depletion (hypotension, tachycardia, dry mucous membranes) 1
- Treatment: volume and sodium replacement, NOT fluid restriction 1, 2
Treatment Approach Based on Symptom Severity
Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)
This is a medical emergency requiring immediate hypertonic saline 1, 3:
- Administer 3% hypertonic saline as 100-150 mL boluses over 10 minutes, repeatable up to 3 times 1
- Target correction of 6 mmol/L over 6 hours or until symptoms resolve 1
- Maximum correction: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 4, 3
- Monitor serum sodium every 2 hours during initial correction 1
Asymptomatic or Mildly Symptomatic Hyponatremia
Treatment depends on volume status 1:
Hypovolemic
- Discontinue diuretics immediately if sodium <125 mmol/L 1
- Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/h initially, then 4-14 mL/kg/h based on response 1
Euvolemic (SIADH)
- Fluid restriction to 1 L/day is first-line treatment 1, 2
- If no response, add oral sodium chloride 100 mEq three times daily 1
- Consider tolvaptan 15 mg once daily (titrate to 30-60 mg) for resistant cases 1, 4
- Urea is an effective alternative treatment 1, 3
Hypervolemic (Heart Failure, Cirrhosis)
- Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L 1, 2
- Discontinue diuretics temporarily if sodium <125 mmol/L 1
- Consider albumin infusion in cirrhotic patients 1
- Avoid hypertonic saline unless life-threatening symptoms present 1
Critical Correction Rate Guidelines
The single most important principle: never exceed 8 mmol/L correction in 24 hours 1, 4, 3:
- Standard correction rate: 4-8 mmol/L per day, maximum 10-12 mmol/L in 24 hours 1
- High-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy): 4-6 mmol/L per day, maximum 8 mmol/L in 24 hours 1, 4
- Overly rapid correction (>12 mEq/L/24 hours) can cause osmotic demyelination syndrome with dysarthria, dysphagia, quadriparesis, seizures, coma, or death 1, 4, 3
Common Pitfalls to Avoid
- Never ignore mild hyponatremia (130-135 mmol/L) – it increases fall risk (21% vs 5%) and mortality (60-fold increase with sodium <130 mmol/L) 1
- Never use fluid restriction in cerebral salt wasting – this worsens outcomes 1, 2
- Never use fluid restriction in subarachnoid hemorrhage patients at risk of vasospasm 1
- Never rely solely on physical examination to determine volume status 1, 2
- Never use hypertonic saline in hypervolemic hyponatremia without life-threatening symptoms 1
- Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours 1, 4, 3
Monitoring During Treatment
- Severe symptoms: check serum sodium every 2 hours during initial correction 1
- Mild symptoms: check serum sodium every 4 hours initially, then daily 1
- Watch for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occurring 2-7 days after rapid correction 1
Management of Overcorrection
If sodium correction exceeds 8 mmol/L in 24 hours 1: