Syndrome of inappropriate antidiuretic hormone medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]

Overview

Treatment of syndrome of inappropriate antidiuretic hormone depends on the etiology. For immediate improvement, all patients with SIADH require strict restriction of their dailywater intake and correction of serum sodium levels. The serum sodium can can be corrected depending on the initial sodium levels of the patient. Mild cases can be managed easily with exclusive fluid restriction. Moderate cases of SIADH are treated with loop diuretics and normal saline, whereas, 3% hypertonic saline may be used in severe cases. In emergency settings, Vasopressin-2 receptor antagonists ( conivaptan ortolvaptan) are used. The definitive treatment of SIADH involves treatment of the underlying condition. Urea, demeclocycline and lithium are also used in the treatment of SIADH

Medical treatment of SIADH

The mainstay of therapy for SIADH

Mild:

• Fluid restriction

Moderate:

• Oral salt tablets with loop diuretics( 20 mg of Furosemide orally twice a day)

Severe:

• 3% hypertonic saline( if sodium level falls below 125meq/l )
• 100 ml of 3% saline, raises sodium by 1.5meq/l in men and 2 meq/l in women
• Goal of rate of increase is an elevation in serum sodium of 4-6 meq/day in the first 2-4 hrs
• The limit is 8meq/day

Emergency setting:

• Vasopressin-2 receptor antagonists such as conivaptan or tolvaptan
• Conivaptan (20mg loading dose followed by continuous infusion of 40mg/day for four days)
• Tolvaptan should not be used longer than thirty days and patients with liver disease

Miscellaneous

• Demeclocycline: Demeclocycline(300-600mg twice a day) is a tetracycline derivative which induces drug-induced diabetes insipidus by acting on the collecting tubule cell to diminish its responsiveness to ADH.The role is limited in emergency care due to the slow onset of action

• Urea: Urea, at a dose of15-30 g/day, increases urinary solute excretion and enhances water excretion

• Special consideration: Hyponatremia is the most common electrolyte abnormality in SIADH. So, the rate at which sodium is corrected is very important in clinical settings. It depends on the degree of hyponatremia, duration (acute or chronic), and symptomatology

− − − − − −

−

−	−
Acute hyponatremia −	Chronic hyponatremia −
− 3% hypertonic saline −	− Fluid restriction −
− Loop diuretics with saline −	− Vasopressin-2 receptor anatgonists −
− Vasopressin-2 receptor antagonists(conivaptan and tolvaptan) −	− Loop diuretics with increased salt intake −
− Water restriction −	− Urea −
−	− Demeclocycline −

−

• Raise serum sodium by 0.5-1 mEq/hr, and not more than 10-12 mEq in the first 24 hours, to avoid complications like osmotic demyelination syndrome

• Raise serum sodium by 0.5-1 mEq/hr, and not more than 10-12 mEq in the first 24 hours, to avoid complications like osmotic demyelination syndrome

• In rare medical emergencies, more commonly seen in cardiology in the context of hypervolemic severe hyponatremia rather than in SIADH
  • Continuous veno-venous hemofiltration (CVVH)
  • Slow, low-efficiency daily dialysis (SLEDD) have been used to improve hyponatremia