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 (SIADH) depends on the etiology. For immediate improvement, all patients with syndrome of inappropriate antidiuretic hormone (SIADH) require strict restriction of their daily water intake and correction of serum sodium levels. The serum sodium 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 or tolvaptan) 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 Therapy

The mainstay of therapy for SIADH include:

1. Mild hyponatremia

1.1. Adults

• Fluid restriction

Note: Fluid intake should be less than the volume of 24-hour urine output and insensible losses.

2. Moderate hyponatremia

2.1. Adults

• Preferred regimen (1) Increase solute intake with 0.25–0.50 g/kg per day of urea
• Alternate regimen (1): Oral salt tablets
• Alternate regimen (2): Furosemide 20 mg PO q12h

Note (1): Do not give demeclocycline, lithium, or vasopressin receptor antagonists. Note (2): Fluid intake should be less than the 24 hour urine output and insensible losses combined

3. Severe hyponatremia

3.1. Adults

• Preferred regimen (1):
  • 3% hypertonic saline (if sodium level falls below 125 mEq/l)
  • 100 ml of 3% saline IV infusion (raises sodium by 1.5 mEq/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 hours to maximum 8 mEq/day.

Note (1): Do not give demeclocycline, lithium, or vasopressin receptor antagonists. Note (2): Fluid intake should be less than the 24 hour urine output and insensible losses combined

4. Emergency setting

4.1. Adults

• Preferred regimen (1): Conivaptan 20 mg loading dose followed by continuous infusion of 40 mg daily for four days
• Preferred regimen (2): Tolvaptan should not be used longer than 30 days in patients with liver disease

5. Miscellaneous

5.1. Adults

• Preferred regimen (1): Demeclocycline 300-600 mg PO q12h
  • 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.

• Preferred regimen (2): Urea 15-30 g PO daily
  • It increases urinary solute excretion and enhances water excretion.

Special considerations

• 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.
• It raises 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.

Treatment of rapid correction of hyponatremia

• Prompt intervention for re-lowering the serum sodium concentration if it increases >10 mmol/l during the first 24 h or >8 mmol/l in any 24 h thereafter.
• Discontinue the ongoing active treatment.
• Consult an expert to discuss if it is appropriate to start an infusion of 10 ml/kg body weight of electrolyte-free water (e.g. glucose solutions) over 1 h under strict monitoring of urine output and fluid balance.
• Consult an expert to discuss if it is appropriate to add intravenous desmopressin 2 μg, ever 8 hours.