From the Guidelines
The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) focuses on treating the underlying cause while addressing hyponatremia, with the most recent and highest quality evidence supporting the use of vasopressin receptor antagonists such as tolvaptan as a key component of treatment 1.
Overview of SIADH Management
The goal of SIADH management is to correct hyponatremia while addressing the underlying cause. This can be achieved through various strategies, including:
- Restricting free water intake
- Increasing free water excretion
- Blocking ADH action at the kidney
Treatment Approaches
For mild to moderate cases (sodium >125 mEq/L), fluid restriction to 800-1000 mL/day is the first-line approach. In more severe or symptomatic cases, 3% hypertonic saline may be administered intravenously at 1-2 mL/kg/hour, with careful monitoring to avoid correcting sodium levels too rapidly (limit correction to <8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome) 1.
Use of Vasopressin Receptor Antagonists
Vasopressin receptor antagonists such as tolvaptan (starting at 15 mg daily, maximum 60 mg) are useful for persistent cases, though require careful monitoring for overcorrection 1. Tolvaptan has been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH.
Other Treatment Options
Other options for chronic management include:
- Salt tablets (1-2 g three times daily)
- Loop diuretics like furosemide (20-40 mg daily)
- Urea (15-60 g/day in divided doses)
- Demeclocycline (300-600 mg twice daily), although it carries a risk of nephrotoxicity
Monitoring and Follow-up
Throughout treatment, frequent monitoring of serum sodium, fluid status, and neurological symptoms is essential to ensure safe and effective management of SIADH.
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 usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma and death
The management of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) includes the use of tolvaptan, a medication that can help increase serum sodium levels. The recommended starting dose is 15 mg once daily, which can be increased to a maximum of 60 mg once daily as needed. It is essential to initiate and re-initiate therapy in a hospital setting to monitor serum sodium levels closely and avoid too rapid correction of hyponatremia, which can lead to serious neurological complications.
- Key considerations:
- Initiate therapy in a hospital setting
- Monitor serum sodium levels closely
- Avoid too rapid correction of hyponatremia
- Increase dose as needed to achieve desired serum sodium level
- Maximum dose: 60 mg once daily 2
From the Research
Management of SIADH
The management of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is largely dependent on the symptomatology of the patient 3, 4. The goal of treatment is to correct hyponatremia and alleviate symptoms.
Treatment Options
- Fluid restriction: This is a common treatment for SIADH, especially for patients with mild to moderate hyponatremia 3, 5, 6, 7.
- Hypertonic saline: This is used to treat severe hyponatremia, especially in patients with acute symptoms 3, 5, 6, 7.
- Vasopressin receptor antagonists (vaptans): These are specific and direct therapy for SIADH, and have been shown to be effective in correcting hyponatremia 3, 5, 6, 4.
- Demeclocycline: This is an antibiotic that can be used to treat SIADH by inducing a state of nephrogenic diabetes insipidus, thereby increasing water excretion 3.
- Urea: This can be used to treat SIADH by increasing water excretion 3.
Algorithm for Treatment
Two algorithms have been developed for the treatment of SIADH-induced hyponatremia:
- Algorithm 1: Addresses acute correction of hyponatremia posing as a medical emergency, and is applicable to both severe euvolemic and hypovolemic hyponatremia 5, 6.
- Algorithm 2: Directed to the therapy of SIADH-induced mild or moderate, non-acute hyponatremia, and addresses when and how to use fluid restriction, solute, furosemide, and tolvaptan to achieve eunatremia in patients with SIADH 5, 6.
Monitoring and Prevention of Complications
It is essential to monitor serum sodium levels closely during treatment to avoid overly rapid correction, which can lead to osmotic demyelination 3, 5, 6, 4, 7. The rate of correction should be limited to less than 8-10 mmol/liter per day. Discontinuation of vaptan therapy should be monitored to prevent hyponatremic relapse, and it may be necessary to taper the vaptan dose or restrict fluid intake or both 3.