How is SIADH syndrome managed?

Management of SIADH Syndrome

Diagnostic Criteria

SIADH is diagnosed by the presence of hyponatremia (serum sodium <134 mEq/L), plasma hypoosmolality (<275 mosm/kg), inappropriately concentrated urine (>500 mosm/kg), and elevated urinary sodium (>20 mEq/L) in a euvolemic patient without hypothyroidism, adrenal insufficiency, or volume depletion. 1

Key diagnostic features include:

• Euvolemic state - absence of edema, orthostatic hypotension, normal skin turgor, and moist mucous membranes 2
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1
• Central venous pressure 6-10 cm H₂O distinguishes SIADH from cerebral salt wasting (CVP <6 cm H₂O) 1

Critical pitfall: Failing to distinguish SIADH from cerebral salt wasting (CSW) in neurosurgical patients leads to dangerous treatment errors, as CSW requires volume replacement while SIADH requires fluid restriction 1, 2

Treatment Algorithm Based on Severity

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

Transfer to ICU immediately and administer 3% hypertonic saline with a target correction of 6 mmol/L over 6 hours or until severe symptoms resolve. 1

• Administer 100 mL boluses of 3% saline over 10 minutes, repeatable up to three times at 10-minute intervals 2
• Monitor serum sodium every 2 hours during initial correction 1
• Never exceed 8 mmol/L total correction in 24 hours to prevent osmotic demyelination syndrome 1, 2
• After initial 6 mmol/L correction, only 2 mmol/L additional correction is permitted in the remaining 18 hours 2

Mild Symptomatic or Asymptomatic Hyponatremia (Sodium <120 mEq/L)

Fluid restriction to 1 L/day is the cornerstone of treatment. 1, 3, 4

• Implement strict fluid restriction to 1000 mL/day 1, 2
• Avoid fluid restriction in the first 24 hours if using tolvaptan to prevent overly rapid correction 5
• If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 2
• Monitor serum sodium every 4 hours initially, then daily 1

Moderate Hyponatremia (Sodium 120-125 mEq/L)

• Fluid restriction to 1-1.5 L/day 2
• Monitor serum electrolytes daily 2
• Consider albumin infusion in hospitalized patients 1

Pharmacological Treatment Options

Second-Line Therapies (When Fluid Restriction Fails)

Demeclocycline is recommended as second-line treatment for chronic SIADH when fluid restriction is ineffective or poorly tolerated. 1, 6

• Induces nephrogenic diabetes insipidus, reducing kidney response to ADH 1
• Long history of use in persistent SIADH cases 1

Tolvaptan (vasopressin receptor antagonist):

• FDA-approved for clinically significant euvolemic hyponatremia 2
• Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 2
• Increases serum sodium by approximately 3.0 mEq/L/day 2
• Critical monitoring: Check sodium at 0,6,24, and 48 hours after initiation to prevent overcorrection 3
• In clinical trials, tolvaptan increased serum sodium significantly more than placebo (4.6 mEq/L difference at Day 30, p<0.0001) 5

Other options include urea (very effective and safe), lithium, and loop diuretics, though these are less commonly used 1, 6

Special Population Considerations

High-Risk Patients (Cirrhosis, Alcoholism, Malnutrition)

These patients require more cautious correction rates of 4-6 mmol/L per day, not exceeding 8 mmol/L in 24 hours. 1, 2

• Higher risk for osmotic demyelination syndrome 1
• Tolvaptan carries 10% risk of GI bleeding in cirrhosis vs. 2% with placebo 2

Neurosurgical Patients

Never use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm. 1, 2

• Consider fludrocortisone 0.1-0.2 mg daily for hyponatremia in SAH patients 1, 2
• Hydrocortisone may prevent natriuresis 2
• Hypertonic saline increases regional cerebral blood flow and brain tissue oxygen in high-grade SAH 2

Cancer Patients (Especially SCLC)

Treatment of the underlying malignancy is essential alongside hyponatremia management. 1

• SIADH occurs in 1-5% of lung cancer patients, particularly SCLC 2
• Hyponatremia usually improves after successful cancer treatment 1
• Chemotherapy agents (cisplatin, vincristine, cyclophosphamide) can worsen hyponatremia 1

Critical Safety Considerations

Prevention of Osmotic Demyelination Syndrome

The absolute maximum correction is 8 mmol/L in any 24-hour period. 1, 2, 3

• Standard correction rate: 4-8 mmol/L per day 2
• High-risk patients: 4-6 mmol/L per day 1, 2
• Symptoms of ODS (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis) typically occur 2-7 days after rapid correction 2

If overcorrection occurs:

• Immediately discontinue current fluids and switch to D5W 2
• Consider desmopressin to slow or reverse rapid sodium rise 2
• Target relowering to bring total 24-hour correction to ≤8 mmol/L 2

Common Pitfalls to Avoid

• Overly rapid correction leading to osmotic demyelination syndrome 1, 2
• Inadequate monitoring during active correction 1, 2
• Using fluid restriction in cerebral salt wasting instead of SIADH - this worsens outcomes 1, 2
• Failing to identify and treat the underlying cause (medications, malignancy, CNS disorders, pulmonary disease) 1, 6
• Ignoring mild hyponatremia (130-135 mmol/L) - even mild hyponatremia increases fall risk (21% vs. 5%) and mortality (60-fold increase) 2
• Using hypotonic fluids (including lactated Ringer's) in SIADH patients - this worsens hyponatremia 2

Medication-Induced SIADH

Discontinue offending medications when possible: 2

• Antidepressants (SSRIs, trazodone) - particularly high risk 2
• Antiepileptics (carbamazepine) 1, 6
• Chemotherapy (cisplatin, vincristine, cyclophosphamide) 1
• NSAIDs, opioids 1
• Chlorpropamide 6