Management Algorithm for SIADH
Diagnostic Confirmation
SIADH is diagnosed by the presence of hypotonic hyponatremia (serum sodium <134 mEq/L), plasma osmolality <275 mosm/kg, inappropriately high urine osmolality (>500 mosm/kg), and inappropriately high urinary sodium (>20 mEq/L) in a euvolemic patient without hypothyroidism, adrenal insufficiency, or volume depletion. 1
Key diagnostic criteria to confirm:
- Euvolemic state (no edema, no orthostatic hypotension, normal skin turgor, moist mucous membranes) 1
- Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2
- Exclude pseudohyponatremia by checking serum glucose and lipids 2
- Rule out hypothyroidism (TSH) and adrenal insufficiency (cortisol) 1
Treatment Algorithm Based on Symptom Severity
SEVERE SYMPTOMATIC HYPONATREMIA (Seizures, Coma, Altered Mental Status)
Transfer to ICU immediately and administer 3% hypertonic saline with a goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve. 1
- Administer 3% hypertonic saline as 100 mL boluses over 10 minutes, repeatable up to 3 times at 10-minute intervals 2
- Total correction MUST NOT exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1, 3
- Monitor serum sodium every 2 hours during initial correction 1
- After symptom resolution, switch to fluid restriction (1 L/day) 1
High-risk populations (advanced liver disease, alcoholism, malnutrition) require even slower correction at 4-6 mmol/L per day 1, 2
MILD SYMPTOMATIC OR ASYMPTOMATIC HYPONATREMIA (Sodium <120 mEq/L)
Implement fluid restriction to 1 L/day as first-line treatment. 1, 4, 5
- Avoid fluid restriction during the first 24 hours to prevent overly rapid correction 3
- Patients can continue fluid intake in response to thirst initially 3
- Monitor serum sodium every 4 hours initially, then daily 1
- If no response to fluid restriction after 24-48 hours, add oral sodium chloride 100 mEq three times daily 1
Pharmacological Options for Chronic/Refractory SIADH
Second-Line Agents (when fluid restriction fails or is poorly tolerated)
Demeclocycline can be considered as second-line treatment for chronic SIADH 1, 5
Tolvaptan (Vasopressin Receptor Antagonist):
- FDA-approved for clinically significant euvolemic hyponatremia 1, 3
- Starting dose: 15 mg once daily, titrate to 30 mg after 24 hours, maximum 60 mg daily 1, 3
- MUST be initiated in hospital with close sodium monitoring 3
- Do not use for more than 30 days due to hepatotoxicity risk 3
- Correction rate with tolvaptan: 3.0 mEq/L/day 1
- Contraindicated with strong CYP3A inhibitors 3
Urea:
- Effective alternative: 30-40 g orally in divided doses 6
- Correction rate: comparable to tolvaptan at 3.0 mEq/L/day 1
- Particularly useful in neurosurgical patients 1
Critical Safety Considerations
Osmotic Demyelination Syndrome Prevention
The maximum correction rate is 8 mmol/L in 24 hours for all patients. 1, 2, 3
- For severe symptoms: correct 6 mmol/L over first 6 hours, then only 2 mmol/L additional in next 18 hours 1
- For high-risk patients (liver disease, alcoholism, malnutrition, prior encephalopathy): limit to 4-6 mmol/L per day 1, 2
If overcorrection occurs:
- Immediately discontinue hypertonic saline and switch to D5W 2
- Consider desmopressin to slow/reverse rapid rise 1, 2
- Watch for osmotic demyelination symptoms (dysarthria, dysphagia, quadriparesis) 2-7 days post-correction 1, 3
Treatment of Underlying Cause
Identifying and treating the underlying disorder is integral to management. 1, 7
Common causes to address:
- Malignancy (especially small cell lung cancer): treat underlying cancer 1
- Medications: discontinue offending agents (SSRIs, carbamazepine, chlorpropamide, cyclophosphamide, vincristine, cisplatin) 1, 5
- CNS disorders: manage underlying neurological condition 8, 7
- Pulmonary diseases: treat lung pathology 8, 7
Special Considerations
Distinguishing SIADH from Cerebral Salt Wasting (CSW)
This distinction is CRITICAL in neurosurgical patients as treatments are opposite. 1, 2
- SIADH: euvolemic, CVP 6-10 cm H₂O → treat with fluid restriction 1
- CSW: hypovolemic, CVP <6 cm H₂O → treat with volume/sodium replacement 1, 2
- Never use fluid restriction in CSW as it worsens outcomes 1, 2
Subarachnoid Hemorrhage Patients
Avoid fluid restriction in patients at risk for vasospasm. 1, 2
Monitoring Protocol
During active correction:
- Severe symptoms: check sodium every 2 hours 1
- Mild symptoms: check sodium every 4 hours 1
- After stabilization: daily monitoring until target reached 1
After discontinuation:
Common Pitfalls to Avoid
- Overly rapid correction (>8 mmol/L/24 hours) causing osmotic demyelination 1, 2
- Inadequate monitoring during active correction 1
- Using fluid restriction in CSW instead of SIADH 1, 2
- Failing to identify and treat underlying cause 1
- Ignoring mild hyponatremia (130-135 mmol/L) which increases fall risk and mortality 2