In an older adult with a traumatic subdural hematoma who develops persistent hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion or cerebral salt‑wasting and cannot tolerate fluid restriction, how should Tolvaptan be initiated, dosed, monitored, and what are the safety limits and alternative treatments?

Tolvaptan in Subdural Hematoma with Persistent Hyponatremia

When to Initiate Tolvaptan

Tolvaptan should only be considered after exhausting standard therapies—fluid restriction (1–1.5 L/day) and temporary discontinuation of diuretics when serum sodium is <125 mmol/L—and only in highly selected patients with severe symptomatic hyponatremia refractory to these measures or when rapid correction is needed before urgent neurosurgical intervention. 1, 2

• Tolvaptan is contraindicated as first-line therapy in subdural hematoma patients; standard volume-status-based management must be attempted first 1, 2
• The drug should be reserved for euvolemic or hypervolemic hyponatremia that persists despite fluid restriction, not for hypovolemic states 1, 2
• In traumatic brain injury with subdural hematoma, distinguish cerebral salt wasting (CSW) from SIADH before considering tolvaptan—CSW requires aggressive volume and sodium replacement with isotonic or hypertonic saline, not fluid restriction or tolvaptan 1

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Dosing Protocol

Start with 7.5 mg orally once daily (half the FDA-approved starting dose) in older adults with traumatic brain injury, as this lower dose effectively increases serum sodium by 7.8 mmol/L within 24 hours while reducing overcorrection risk. 3

• The FDA-approved starting dose is 15 mg once daily, which may be increased to 30 mg after ≥24 hours and to a maximum of 60 mg daily as needed 4
• However, in younger patients (<40 years) with normal renal function (creatinine <1.0 mg/dL), even 15 mg can cause dangerously rapid correction (up to 1 mmol/L per hour), so consider starting at 3.75–7.5 mg 5, 3
• Tolvaptan must be initiated and re-initiated only in a hospital setting where serum sodium can be monitored closely 4
• Do not apply fluid restriction during the first 24 hours of tolvaptan therapy, as this increases the risk of over-rapid sodium correction 1

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Intensive Monitoring Requirements

Check serum sodium every 2 hours during the first 8 hours after the initial dose, then every 4–6 hours while on therapy, to ensure the correction rate does not exceed 8 mmol/L in any 24-hour period. 1, 2, 6

Parameter	Frequency	Rationale
Serum sodium	Every 2 hours for first 8 hours, then every 4–6 hours	Detect overcorrection early; 23% of patients with baseline sodium <125 mmol/L experience excessive correction [6]
Liver function tests (ALT, AST, bilirubin)	Baseline and monthly	4.4% of patients develop ALT >3× upper limit of normal [1]
Clinical assessment (weight, fluid balance, neurologic exam)	Daily	Identify volume shifts and early signs of osmotic demyelination [1]

• For every 1 mmol/L reduction in baseline sodium, expect an additional 0.23 mmol/L increase in 24-hour correction—patients with starting sodium <125 mmol/L are at highest risk for overcorrection 6
• Monitor for signs of osmotic demyelination syndrome (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically 2–7 days after rapid correction 1, 4

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Safety Limits and Correction Targets

Never exceed a sodium rise of 8 mmol/L in any 24-hour period; in older adults with traumatic brain injury, advanced liver disease, alcoholism, or malnutrition, limit correction to 4–6 mmol/L per day. 1, 2, 4

• The FDA boxed warning states that too rapid correction (>12 mEq/L per 24 hours) can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death 4
• In susceptible patients (severe malnutrition, alcoholism, advanced liver disease), slower rates of correction are advisable 4
• The therapeutic goal is serum sodium of 125–130 mmol/L, not normalization to 135–145 mmol/L 1

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Management of Overcorrection

If serum sodium rises excessively (>8 mmol/L in 24 hours), immediately stop tolvaptan and administer 5% dextrose in water (D5W) or desmopressin to lower the sodium level back to ≤8 mmol/L total increase from baseline. 1, 2

• Desmopressin can slow or reverse a rapid sodium rise 1
• The corrective target is to bring the total 24-hour increase back to ≤8 mmol/L from the starting point 1

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Duration of Therapy

Limit tolvaptan use to ≤30 days, as long-term use is associated with increased hepatotoxicity and all-cause mortality in patients with reduced liver function. 1

• Tolvaptan should be discontinued once serum sodium stabilizes at 125–130 mmol/L and the patient can tolerate fluid restriction 1, 2
• In the two reported cases of recurrent SIAD after traumatic brain injury, tolvaptan 7.5 mg daily (or every other day) was required for sustained normalization, but these represent exceptional circumstances requiring ongoing specialist supervision 7

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Alternative Treatments When Tolvaptan Cannot Be Tolerated

If tolvaptan causes excessive correction or is contraindicated, alternative pharmacologic options for SIADH include oral sodium chloride (100 mEq three times daily), urea, loop diuretics, demeclocycline, or lithium, all combined with fluid restriction to 1 L/day. 1, 2

• For cerebral salt wasting (not SIADH), the treatment is fundamentally different: aggressive volume and sodium replacement with isotonic saline (50–100 mL/kg/day) or hypertonic saline (3% NaCl) for severe cases, plus fludrocortisone 0.1–0.2 mg daily 1
• Fluid restriction must never be used in cerebral salt wasting, as it worsens outcomes and can precipitate cerebral ischemia 1
• In subarachnoid hemorrhage patients at risk for vasospasm, avoid fluid restriction and consider fludrocortisone or hydrocortisone to prevent natriuresis 1

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Critical Pitfalls to Avoid

• Using tolvaptan as first-line therapy before standard measures (fluid restriction, diuretic discontinuation) 1
• Applying fluid restriction during the first 24 hours of tolvaptan, which increases overcorrection risk 1
• Failing to distinguish CSW from SIADH in traumatic brain injury—CSW requires volume expansion, not tolvaptan 1
• Using the full 15 mg starting dose in younger patients (<40 years) with normal renal function, which can cause dangerously rapid correction 5, 3
• Extending treatment beyond 30 days, which raises hepatotoxicity risk 1
• Failing to monitor liver function monthly during therapy 1
• Correcting serum sodium faster than 4–6 mmol/L per day in high-risk patients (older adults, alcoholism, malnutrition, liver disease) 1, 4

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Special Considerations in Subdural Hematoma

• 3% hypertonic saline remains the preferred acute treatment for severe symptomatic hyponatremia (seizures, coma, altered mental status) in subdural hematoma patients, with a target correction of 6 mmol/L over 6 hours 2
• Tolvaptan is not a substitute for hypertonic saline in neurologic emergencies 2
• In subdural hematoma with elevated intracranial pressure, 3% hypertonic saline (100 mL boluses over 10 minutes, up to three times) reduces ICP and improves cerebral perfusion pressure more rapidly than tolvaptan 1
• Fluid restriction is contraindicated in subdural hematoma patients with hyponatremia, as it can worsen cerebral perfusion 1

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Evidence Quality and Guideline Perspective

• European guidelines do not recommend tolvaptan for SIADH, principally due to concerns about overcorrection risk 6
• The real-life effectiveness data show that 23% of patients with baseline sodium <125 mmol/L experience excessive correction (≥10 mmol/L in 24 hours), though no cases of osmotic demyelination syndrome were recorded in one UK series 6
• Low-dose tolvaptan (3.75–7.5 mg) effectively increases serum sodium by 7.1–7.8 mmol/L within 24 hours with lower overcorrection rates than the standard 15 mg dose 3
• The evidence supports initiating tolvaptan at 7.5 mg, or 3.75 mg in high-risk patients, with close monitoring of sodium levels 3