What is the management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

From the Guidelines

Management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should prioritize treating the underlying cause while addressing hyponatremia, with fluid restriction and pharmacological options like vasopressin receptor antagonists being key components of treatment, as supported by the most recent and highest quality study 1. The approach to managing SIADH involves:

• For mild to moderate cases with minimal symptoms, fluid restriction to 800-1000 mL/day is the first-line approach.
• In more severe cases (sodium <120 mEq/L) or when patients are symptomatic, hypertonic (3%) saline may be administered intravenously at 1-2 mL/kg/hour, with careful monitoring to avoid correcting sodium too rapidly (limit correction to 8-10 mEq/L in 24 hours to prevent osmotic demyelination syndrome) 1.
• For chronic SIADH, pharmacological options include salt tablets (1-2 g three times daily), oral urea (30 g daily), and vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily, titrating up to 60 mg if needed), as these have been shown to be effective in improving serum sodium concentration in conditions associated with high vasopressin levels, such as SIADH 1.
• Loop diuretics such as furosemide (20-40 mg daily) can enhance free water excretion when combined with salt supplementation.
• Demeclocycline (300-600 mg twice daily) may be used as a third-line agent due to potential nephrotoxicity. Throughout treatment, frequent monitoring of serum sodium, fluid status, and neurological symptoms is essential, with the goal of gradually normalizing sodium levels while addressing the underlying cause, which might include discontinuing contributing medications, treating infections, or addressing malignancies that may be triggering SIADH 1.

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.

The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) with tolvaptan involves:

• Initiating and re-initiating treatment in a hospital where serum sodium can be closely monitored
• Starting with a dose of 15 mg once daily, increasing to 30 mg once daily after at least 24 hours, and up to a maximum of 60 mg once daily as needed
• Avoiding fluid restriction during the first 24 hours of therapy
• Monitoring serum sodium and volume status closely to avoid too rapid correction of hyponatremia 2

From the Research

Management of SIADH

The management of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) involves various treatment options, including:

• Fluid restriction: considered the first-line therapy for mild and asymptomatic hyponatremia, with an initial fluid restriction of 500 ml/day adjusted according to serum sodium levels 3
• Hypertonic saline: used for acute correction of hyponatremia, particularly in severe cases, with a 3% sodium chloride solution administered as a 100- to 150-ml intravenous bolus or continuous infusion 3, 4, 5
• Urea: considered an effective and safe treatment for SIADH, particularly in patients who do not respond to fluid restriction 3
• Tolvaptan: a vasopressin-2 receptor antagonist, considered a potent pharmacological tool for targeting the underlying pathophysiology of SIADH, with clinical efficacy supported by good quality randomized, placebo-controlled clinical trials 3, 5
• Conivaptan: an intravenous vasopressin-receptor antagonist, used for refractory SIADH, particularly in pediatric patients 6
• Vaptans: vasopressin receptor antagonists, targeted specifically for the correction of euvolemic hyponatremia, used as an alternative to fluid restriction and hypertonic saline 4, 7

Treatment Algorithms

Two algorithms have been developed for the management of SIADH:

• Algorithm 1: addresses acute correction of hyponatremia, using 3% hypertonic saline solution, with specific infusion rates and steps to avoid or reverse overcorrection of serum sodium levels 4
• Algorithm 2: directed to the therapy of SIADH-induced mild or moderate, non-acute hyponatremia, using fluid restriction, solute, furosemide, and tolvaptan to achieve eunatremia in patients with SIADH 4

Monitoring and Readiness

Close monitoring and readiness for administration of either hypotonic fluids or desmopressin are crucial in the decision-making process for specific treatment and eventual overcorrection consequences 3