Pediatric Cardiology

, Volume 34, Issue 6, pp 1463–1468 | Cite as

Tolvaptan Increases Serum Sodium in Pediatric Patients With Heart Failure

  • Rebecca B. Regen
  • Ashley Gonzalez
  • Kasey Zawodniak
  • David Leonard
  • Raymond Quigley
  • Aliessa P. Barnes
  • Joshua D. KochEmail author
Original Article


This study aimed to evaluate the use of tolvaptan in a consecutive series of pediatric patients with heart failure. Patients 18 years of age or younger with heart failure prescribed tolvaptan between January 2009 and October 2011 were retrospectively identified at Children’s Medical Center Dallas. Laboratory parameters, urine output, fluid balance, and concurrent medications were recorded at baseline and at specified intervals after a single dose of tolvaptan. The 28 patients in the study had a median age of 2 years (range 1 month–18 years). The median tolvaptan dose administered was 0.3 mg/kg (range 0.1–1.3 mg/kg). The study patients had a median baseline serum sodium concentration of 127 mmol/L, and the increases in sodium were 2.5 mmol/L at 12 h, 5 mmol/L at 24 h, 4 mmol/L at 48 h, and 5 mmol/L at 72 h (all p < 0.001). Urine output was increased at 24 h (p < 0.001) and 48 h (p = 0.03), and fluid balance changes were significantly different at 24 h (p = 0.004). The changes in potassium, blood urea nitrogen, and serum creatinine were not significant at any interval. When controlling for traditional diuretic therapy, increases in serum sodium concentration and urine output remained statistically significant. A single dose of tolvaptan increased serum sodium concentrations for the majority in this small series of pediatric patients with heart failure. These results suggest that tolvaptan can be safely and effectively administered to pediatric patients. Prospective, randomized controlled trials are needed to evaluate the safety and efficacy of its use further.


Diuretics Heart failure Hyponatremia Pediatrics Sodium 


  1. 1.
    Berl T, Quittnat-Pelletier F, Verbalis JG et al (2010) Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol 21:705–712PubMedCrossRefGoogle Scholar
  2. 2.
    Costello-Boerrigter LC, Smith WB, Boerrigter G et al (2006) Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol 290:F273–F278PubMedCrossRefGoogle Scholar
  3. 3.
    Decaux G, Soupart A, Vassart G (2008) Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet 371:1624–1632PubMedCrossRefGoogle Scholar
  4. 4.
    Gheorghiade M, Niazi I, Ouyang J et al (2003) Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107:2690–2696PubMedCrossRefGoogle Scholar
  5. 5.
    Gheorghiade M, Abraham WT, Albert NM et al (2007) Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J 28:980–988PubMedCrossRefGoogle Scholar
  6. 6.
    Goldsmith SR (2005) Current treatments and novel pharmacologic treatments for hyponatremia in congestive heart failure. Am J Cardiol 95:14B–23BPubMedCrossRefGoogle Scholar
  7. 7.
    Goldsmith SR, Francis GS, Cowley AW Jr et al (1983) Increased plasma arginine vasopressin levels in patients with congestive heart failure. J Am Coll Cardiol 1:1385–1390PubMedCrossRefGoogle Scholar
  8. 8.
    Greenberg A (2000) Diuretic complications. Am J Med Sci 319:10–24PubMedCrossRefGoogle Scholar
  9. 9.
    Jao GT, Chiong JR (2010) Hyponatremia in acute decompensated heart failure: mechanisms, prognosis, and treatment options. Clin Cardiol 33:666–671PubMedCrossRefGoogle Scholar
  10. 10.
    Jones RC, Rajasekaran S, Rayburn M et al (2012) Initial experience with conivaptan use in critically ill infants with cardiac disease. J Pediatr Pharmacol Ther 17:78–83PubMedGoogle Scholar
  11. 11.
    Kazory A (2010) Hyponatremia in heart failure: revisiting pathophysiology and therapeutic strategies. Clin Cardiol 33:322–329PubMedCrossRefGoogle Scholar
  12. 12.
    Konstam MA, Gheorghiade M, Burnett JC Jr et al (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial. JAMA 297:1319–1331PubMedCrossRefGoogle Scholar
  13. 13.
    Krumholz HM, Chen Y, Bradford WD et al (1999) Variations in and correlates of length of stay in academic hospitals among patients with heart failure resulting from systolic dysfunction. Am J Manag Care 5:715–723PubMedGoogle Scholar
  14. 14.
    Lee DS, Austin PC, Rouleau JL et al (2003) Predicting mortality among patients hospitalized for heart failure. JAMA 290:2581–2587PubMedCrossRefGoogle Scholar
  15. 15.
    Nemerovski C, Hutchinson DJ (2010) Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review. Clin Ther 32:1015–1032PubMedCrossRefGoogle Scholar
  16. 16.
    Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan (2009) Samsca™ (tolvaptan) (package insert)Google Scholar
  17. 17.
    Rianthavorn P, Cain JP, Turman MA (2008) Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH. Pediatr Nephrol 23:1367–1370PubMedCrossRefGoogle Scholar
  18. 18.
    Sahu R, Balaguru D, Thapar V et al (2012) Conivaptan therapy in an infant with severe hyponatremia and congestive heart failure. Tex Heart Inst J 39:724–726PubMedGoogle Scholar
  19. 19.
    Schrier RW, Gross P, Gheorghiade M et al (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 355:2099–2112PubMedCrossRefGoogle Scholar
  20. 20.
    Tribouilloy C, Buiciuc O, Rusinaru D et al (2010) Long-term outcome after a first episode of heart failure: a prospective 7-year study. Int J Cardiol 140:309–314PubMedCrossRefGoogle Scholar
  21. 21.
    Yi J, Shin H, Kim H (2011) V2 receptor antagonist, tolvaptan. Electrolyte Blood Press 9:50–54PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rebecca B. Regen
    • 1
  • Ashley Gonzalez
    • 1
  • Kasey Zawodniak
    • 1
  • David Leonard
    • 2
  • Raymond Quigley
    • 1
    • 3
  • Aliessa P. Barnes
    • 1
    • 3
  • Joshua D. Koch
    • 1
    • 3
    Email author
  1. 1.Children’s Medical CenterDallasUSA
  2. 2.Department of Clinical SciencesUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.Department of PediatricsUniversity of Texas Southwestern Medical CenterDallasUSA

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