In a patient with an acute intracranial insult such as subarachnoid hemorrhage who develops hyponatremia, how can I differentiate cerebral salt‑wasting syndrome from the syndrome of inappropriate antidiuretic hormone secretion and what is the appropriate management?

Differentiating Cerebral Salt Wasting from SIADH in Acute Intracranial Injury

In a patient with subarachnoid hemorrhage or other acute brain injury who develops hyponatremia, the critical distinction between cerebral salt wasting (CSW) and SIADH hinges on volume status: CSW presents with true hypovolemia requiring aggressive sodium and volume replacement, while SIADH presents with euvolemia requiring fluid restriction—applying the wrong treatment can be fatal. 1, 2

Diagnostic Approach: Volume Status is Decisive

Clinical Assessment of Volume Status

The single most important diagnostic step is determining whether the patient is hypovolemic (CSW) or euvolemic (SIADH), as these conditions require opposite treatments. 1, 2

Physical examination alone has poor accuracy (sensitivity 41%, specificity 80%), so you must integrate multiple clinical parameters 1, 3:

Signs of hypovolemia (CSW):

• Orthostatic hypotension and tachycardia 1, 2
• Dry mucous membranes and decreased skin turgor 1, 2
• Flat neck veins 1, 4
• Central venous pressure <6 cm H₂O (if available) 1, 3
• Evidence of negative fluid balance 2, 5

Signs of euvolemia (SIADH):

• Normal blood pressure without orthostatic changes 1, 6
• Moist mucous membranes 1
• Normal skin turgor 1
• Central venous pressure 6-10 cm H₂O 1, 3
• No edema, no signs of dehydration 6, 2

Laboratory Findings (Overlapping but Supportive)

Both conditions share several laboratory features, which is why volume assessment is paramount 1, 2:

Common to both CSW and SIADH:

• Serum sodium <135 mmol/L (investigate when <131 mmol/L) 1, 6
• Urine sodium >20-40 mmol/L 1, 3, 2
• Urine osmolality >300-500 mOsm/kg 1, 3
• Low serum osmolality <275 mOsm/kg 6, 3

Distinguishing features:

• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH (though can also occur in CSW) 1, 3
• Blood urea nitrogen and creatinine may be elevated in CSW due to volume depletion 1
• Hematocrit may be elevated in CSW due to hemoconcentration 2, 5

Do NOT order plasma ADH or natriuretic peptide levels—these are not supported by evidence and delay treatment. 1, 3

Management: Opposite Treatments for Opposite Conditions

Treatment of Cerebral Salt Wasting (Hypovolemic)

CSW requires aggressive volume and sodium replacement; fluid restriction will worsen outcomes and can precipitate cerebral ischemia. 1, 2, 5

For non-severe CSW:

• Isotonic saline (0.9% NaCl) at 50-100 mL/kg/day 1, 5
• Target central venous pressure 8-12 cm H₂O 1
• Monitor urine output and replace ongoing sodium losses 2, 5

For severe symptomatic CSW (seizures, altered mental status):

• ICU admission with 3% hypertonic saline 1, 2
• Target correction of 6 mmol/L over first 6 hours or until symptoms resolve 1
• Maximum correction 8 mmol/L in any 24-hour period 1, 2
• Check serum sodium every 2 hours during initial correction 1

Adjunctive pharmacotherapy:

• Fludrocortisone 0.1-0.2 mg daily for severe or refractory CSW 1, 7, 5
• Hydrocortisone may prevent natriuresis in subarachnoid hemorrhage patients 1, 2

Treatment of SIADH (Euvolemic)

SIADH requires fluid restriction as first-line therapy; volume expansion will worsen the condition. 1, 6, 2

For mild-moderate SIADH:

• Fluid restriction to ≤1 L/day 1, 6, 2
• If no response, add oral sodium chloride 100 mEq three times daily 1
• Monitor serum sodium every 24-48 hours initially 6

For severe symptomatic SIADH (sodium <120 mmol/L with neurological symptoms):

• 3% hypertonic saline with target correction of 6 mmol/L over 6 hours 1, 6
• Maximum correction 8 mmol/L in 24 hours 1, 6
• Check serum sodium every 2 hours during correction 1, 6

Second-line pharmacological options for refractory SIADH:

• Demeclocycline 6
• Urea 1, 6
• Loop diuretics 1
• Vasopressin receptor antagonists (tolvaptan) 6

Special Considerations in Subarachnoid Hemorrhage

In SAH patients at risk for vasospasm, never use fluid restriction even if SIADH is suspected—treat presumptively as CSW with volume expansion to prevent cerebral ischemia. 1, 6, 2

Fludrocortisone and hydrocortisone may be used prophylactically in SAH to prevent vasospasm and reduce natriuresis 1, 6, 2.

Critical Safety Considerations

Never correct serum sodium faster than 8 mmol/L in any 24-hour period to prevent osmotic demyelination syndrome. 1, 6, 2 Signs of osmotic demyelination (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically appear 2-7 days after rapid correction 1.

The most dangerous pitfall is misdiagnosing CSW as SIADH and applying fluid restriction—this worsens hypovolemia, increases cerebral ischemia risk, and can be fatal in neurosurgical patients. 1, 2, 4

When volume status is uncertain in a neurosurgical patient, particularly with SAH, err on the side of treating as CSW with volume expansion rather than risking cerebral ischemia from inappropriate fluid restriction 1, 2.