From the Guidelines
To screen for SIADH, hyponatremia (serum sodium < 134 mEq/L) with hypoosmolality (plasma osmolality < 275 mosm/kg), inappropriately high urine osmolality (> 500 mosm/kg), and elevated urine sodium concentration (> 20 mEq/L) should be assessed in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism 1.
Diagnostic Criteria
The diagnostic criteria for SIADH include:
- Hyponatremia (serum sodium < 134 mEq/L)
- Hypoosmolality (plasma osmolality < 275 mosm/kg)
- Inappropriately high urine osmolality (> 500 mosm/kg)
- Inappropriately high urinary sodium concentration (> 20 mEq/L)
- Absence of hypothyroidism or adrenal insufficiency or volume depletion
Treatment Options
Treatment options for SIADH depend on the severity of symptoms and sodium levels.
- For mild, asymptomatic cases, fluid restriction to less than 1 L/day is recommended 1.
- For moderate hyponatremia, pharmacologic options include vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily) or demeclocycline (300-600 mg twice daily) 1.
- For severe, symptomatic hyponatremia (sodium < 120 mEq/L with neurological symptoms), 3% hypertonic saline should be administered at 1-2 mL/kg/hour with careful monitoring to raise sodium by 4-6 mEq/L in the first 4-6 hours, not exceeding 8-10 mEq/L in 24 hours to avoid osmotic demyelination syndrome 1. It is essential to address the underlying cause of SIADH, such as medications, pulmonary disease, CNS disorders, or malignancy, for long-term management. Regular monitoring of serum sodium, fluid status, and neurological symptoms is crucial during treatment.
From the FDA Drug Label
Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
The diagnostic criteria for SIADH include:
- Hyponatremia: serum sodium <135 mEq/L
- Euvolemic: patient has a normal or slightly increased extracellular fluid volume
- Inability to suppress ADH: patient has an elevated ADH level despite hyponatremia
- Absence of other causes of hyponatremia: patient does not have heart failure, liver cirrhosis, or other conditions that can cause hyponatremia
The treatment options for SIADH include:
- Fluid restriction: limiting fluid intake to <1.0 liter/day
- Tolvaptan: a vasopressin receptor antagonist that can help increase serum sodium levels
- Monitoring: close monitoring of serum sodium levels and volume status to avoid overly rapid correction of hyponatremia 2, 2, 2
From the Research
Diagnostic Criteria for SIADH
- The diagnosis of SIADH should be considered if the five cardinal criteria are fulfilled:
- Hypotonic hyponatraemia
- Natriuresis
- Urine osmolality in excess of plasma osmolality
- Absence of oedema and volume depletion
- Normal renal and adrenal function 3
- Clinical euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality, and exclusion of pseudohyponatraemia and diuretic use 4
- Patients' extensive medical history and structured physical and biochemical tests are considered the milestones marking the way of the SIADH management 5
Treatment Options for SIADH
- Fluid restriction of 800-1200 mL/24 hours is the mainstay of treatment 4, 3
- Hypertonic saline for patients with severe hyponatraemia and symptoms of altered mental state or seizures 4
- Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH 6
- Urea and demeclocycline are also used as therapeutic modalities 6
- The most common monotherapy treatments for hyponatremia in SIADH were fluid restriction, isotonic or hypertonic saline, and tolvaptan 7
Important Considerations in SIADH Treatment
- Limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 6, 4
- Monitor serum sodium levels closely, especially in the first 24 hours of treatment with vaptans 6
- Discontinuation of any vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse 6
- Appropriate laboratory tests to diagnose SIADH were obtained in <50% of patients, and success rates in correcting hyponatremia were significantly higher when such tests were obtained 7