Abstract: FR-PO663
Tolvaptan Resistance in Severe SIADH
Session Information
- Fluid and Electrolytes: Clinical - Potassium, Sodium, Water
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid and Electrolytes
- 902 Fluid and Electrolytes: Clinical
Author
- Segal, Alan, University of Vermont, Burlington, Vermont, United States
Introduction
Approaches to treat euvolemic hyponatremia include: 1) minimizing input of hypotonic solutions (restricting positive free water); 2) administering hypertonic solutions (giving negative free water); 3) decreasing the driving force for electrolyte-free water reabsorption by a) increasing the urinary solute load (oral urea, NaCl, KCl) and b) decreasing medullary concentration (loop diuretics); and 4) decreasing the permeability for electrolyte-free water reabsorption (demeclocycline, vaptan aquaretics). The recent introduction of tolvaptan provides a molecular tool to essentially treat the syndrome of inappropriate anti-diuretic hormone (SIADH) secretion with “nephrogenic DI in a bottle.” We present a case where all of these approaches were utilized.
Case Description
A 48-year-old man developed severe hyponatremia (serum [Na] 107 mM) due to SIADH in the setting of recurrent metastatic small cell lung cancer. He was asymptomatic. Oral fluid restriction and 3% NaCl were employed to gradually increase his serum [Na] to 125 mM over 4 days. He was then placed on tolvaptan 15 mg daily without effect, so the dose was increased to 30 mg daily and he was discharged home 2 days later with a serum [Na] of 131 mM.
Over the next 4 days, serum [Na] decreased to 127 mM and 3 days later he felt “off” and was re-admitted with serum [Na] 117 mM. Tolvaptan was increased to 60 mg daily—and ultimately to 60 mg twice daily—without effect, as urine osmolality remained >900 mosm/kgH2O. Serum [Na] increased sluggishly to 122 mM two days later but then decreased again to 117 mM.
Tolvaptan was discontinued and he was placed on NaCl tablets 2 g tid, KCl 20 mmoles twice daily, and furosemide 40 mg twice daily. Over the next 3 days, serum [Na] increased to 124 mM. Oral urea 15 g twice daily was started and serum [Na] only increased to 126 mM, so the dose was increased to 30 g twice daily, and over the next 4 days serum [Na] increased to 140 mM. The patient has since maintained isotonicity on twice daily use of urea 30 g, NaCl 2 g, KCl 20 mmoles, and furosemide 40 mg.
Discussion
This case illustrates that a patient with severe SIADH may be resistant to a maximal dose of tolvaptan yet still respond to traditional measures. Therefore, while aquaretic therapy aimed at the underlying free water permeability defect may be more physiologically elegant, maneuvers that modify the driving force for electrolyte-free water reabsorption may be more practical.