Syndrome of Inappropriate Antidiuretic Hormone Secretion - Management

Management

Management of SIADH includes:

• Treating underlying causes when possible.
• Long-term fluid restriction of 1,200–1,800 mL/day will increase serum sodium through decreasing total body water.
• For very symptomatic patients (severe confusion, convulsions, or coma) hypertonic saline (3%) 1-2 ml/kg IV in 3-4 h should be given.
• Drugs
  • Demeclocycline can be used in chronic situations when fluid restrictions are difficult to maintain; demeclocycline is the most potent inhibitor of Vasopressin (ADH/AVP) action. However, demeclocycline has a 2-3 delay in onset with extensive side effect profile, including but not limited to new onset Nephrogenic Diabetes Insipidus (70%), skin photosensitivity, and nephrotoxicity.
  • Urea: oral daily ingestion has shown favorable long-term results with protective effects in myelinosis and brain damage. Limitations noted to be undesirable taste and is contraindicated in patients with cirrhosis to avoid initiation or potentiation of hepatic encephalopathy.
  • Conivaptan - an antagonist of both V_1A and V₂ vasopressin receptors. Its indications are "treatment of euvolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.". Conivaptan, however, is only available as a parenteral preparation.
  • Tolvaptan - an antagonist of the V₂ vasopressin receptor. A randomized controlled trial showed tolvaptan is able to raise serum sodium in patients with euvolemic or hypervolemic hyponatremia in 2 different tests. Combined analysis of the 2 trials showed an improvement in hyponatremia in both the short term (primary sodium change in average AUC: 3.62+/- 2.68 and 4.35 +/-2.87) and long term with long term maintenance (primary sodium change in average AUC: 6.22 +/- 4.22 and 6.20 +/- 4.92), at 4 days and 30 days, respectively. Tolvaptan’s side effect profile is minimal. Discontinuation of the Tolvaptan showed return of hyponatremia to control values at their respective time frames.

No head to head study is currently available to quantify and compare the relative efficacies of V2 vasopressin receptor antagonists with demeclocycline or other treatment options.

Care must be taken when correcting hyponatremia. A rapid rise in the sodium level may cause central pontine myelinolysis. Avoid correction by more than 12 mEq/L/day. Initial treatment with hypertonic saline may abruptly lead to a rapid dilute diuresis and fall in ADH. Rapid diuresis may lead to over-rapid rise in serum sodium, and should be managed with extreme care.