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Published in: Internal and Emergency Medicine 7/2017

01-10-2017 | EM - ORIGINAL

Efficacy and safety of two different tolvaptan doses in the treatment of hyponatremia in the Emergency Department

Authors: Luigi Mario Castello, Marco Baldrighi, Alice Panizza, Ettore Bartoli, Gian Carlo Avanzi

Published in: Internal and Emergency Medicine | Issue 7/2017

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Abstract

Hyponatremia (plasma sodium concentration or P[Na+] <136 mEq/L) is the most common electrolyte unbalance in clinical practice. Although it constitutes a negative prognostic factor, it frequently remains underdiagnosed and undertreated. Tolvaptan is an oral V2-receptor antagonist which produces aquaresis. Given its emerging role in the treatment of dilutional hyponatremia, we aimed to compare the efficacy and safety of two different doses of this drug in an Emergency Department (ED) setting. Consecutive patients with moderate–severe euvolemic or hypervolemic hyponatremia were sequentially assigned to the 15 mg Group and to the 7.5 mg Group, and were revaluated at 6, 12 and 24 h. Further evaluations and administrations were scheduled daily until P[Na+] correction was achieved or the maximum period of 72 h was exceeded. A 1-month follow-up was performed. Twenty-three patients were enrolled: 12 were included in the 15 mg Group, 11 in the 7.5 mg Group. Both doses significantly elevated the P[Na+] over 24 h, although the 15 mg Group showed faster corrections than the 7.5 mg Group (12 vs 6 mEq/L/24 h; P = 0.025). An optimal correction rate (within 4–8 mEq/L/24 h) was observed in 45.4 % of the 7.5 mg Group against 25.0 % (P n.s.). The standard dose led to dangerous overcorrections (>12 mEq/L/24 h) in 41.7 % of the patients, while the low dose did not cause any (P = 0.037). No osmotic demyelination syndrome was observed. A 7.5 mg tolvaptan dose can be considered both effective and safe in treating hyponatremia in the ED, while a 15 mg dose implicates too high risk of overcorrection.
Literature
2.
go back to reference Upadhyay A, Jaber BL, Madias NE (2006) Incidence and prevalence of hyponatremia. Am J Med 119(7):S30–S35CrossRefPubMed Upadhyay A, Jaber BL, Madias NE (2006) Incidence and prevalence of hyponatremia. Am J Med 119(7):S30–S35CrossRefPubMed
3.
go back to reference Hoorn EJ, Lindemans J, Zietse R (2006) Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant 21(1):70–76CrossRefPubMed Hoorn EJ, Lindemans J, Zietse R (2006) Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant 21(1):70–76CrossRefPubMed
4.
go back to reference Hawkins RC (2003) Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta 337(1–2):169–172CrossRefPubMed Hawkins RC (2003) Age and gender as risk factors for hyponatremia and hypernatremia. Clin Chim Acta 337(1–2):169–172CrossRefPubMed
5.
go back to reference Bartoli E, Castello L, Fumo E, Pirisi M (2002) Electrolyte derangements and diuretic misuse in the elderly. Arch Gerontol Geriatr Suppl 8:43–52CrossRefPubMed Bartoli E, Castello L, Fumo E, Pirisi M (2002) Electrolyte derangements and diuretic misuse in the elderly. Arch Gerontol Geriatr Suppl 8:43–52CrossRefPubMed
6.
go back to reference Hannon MJ, Thompson CJ (2010) The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol 162(1):S5–S12CrossRefPubMed Hannon MJ, Thompson CJ (2010) The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol 162(1):S5–S12CrossRefPubMed
7.
8.
go back to reference Verbalis JG (2010) Brain volume regulation in response to changes in osmolality. Neuroscience 168(4):862–870CrossRefPubMed Verbalis JG (2010) Brain volume regulation in response to changes in osmolality. Neuroscience 168(4):862–870CrossRefPubMed
9.
go back to reference Corona G, Giuliani C, Parenti G et al (2013) Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis. PLoS One 8(12):e80451CrossRefPubMedPubMedCentral Corona G, Giuliani C, Parenti G et al (2013) Moderate hyponatremia is associated with increased risk of mortality: evidence from a meta-analysis. PLoS One 8(12):e80451CrossRefPubMedPubMedCentral
10.
go back to reference Amin A, Deitelzweig S, Christian R et al (2012) Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US. J Hosp Med 7(8):634–639CrossRefPubMed Amin A, Deitelzweig S, Christian R et al (2012) Evaluation of incremental healthcare resource burden and readmission rates associated with hospitalized hyponatremic patients in the US. J Hosp Med 7(8):634–639CrossRefPubMed
11.
go back to reference Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G (2006) Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 119(1):71.e1–8 Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G (2006) Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 119(1):71.e1–8
12.
13.
go back to reference Spasovski G, Vanholder R, Allolio B et al (2014) Clinical practice guideline on diagnosis and treatment of hyponatremia. Nephrol Dial Transplant 29(2):i1–i39CrossRefPubMed Spasovski G, Vanholder R, Allolio B et al (2014) Clinical practice guideline on diagnosis and treatment of hyponatremia. Nephrol Dial Transplant 29(2):i1–i39CrossRefPubMed
14.
go back to reference Castello L, Pirisi M, Sainaghi PP, Bartoli E (2005) Hyponatremia in liver cirrhosis: pathophysiological principles of management. Dig Liver Dis 37(2):73–81CrossRefPubMed Castello L, Pirisi M, Sainaghi PP, Bartoli E (2005) Hyponatremia in liver cirrhosis: pathophysiological principles of management. Dig Liver Dis 37(2):73–81CrossRefPubMed
15.
16.
go back to reference Fenske W, Maier SK, Blechschmidt A, Allolio B, Störk S (2010) Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study. Am J Med 123(7):652–657CrossRefPubMed Fenske W, Maier SK, Blechschmidt A, Allolio B, Störk S (2010) Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study. Am J Med 123(7):652–657CrossRefPubMed
17.
go back to reference Bartoli E, Castello L, Sainaghi PP (2003) Diagnosis and therapy of hyponatremia. Ann Ital Med Int 18(4):193–203 Bartoli E, Castello L, Sainaghi PP (2003) Diagnosis and therapy of hyponatremia. Ann Ital Med Int 18(4):193–203
18.
go back to reference Riegger GA, Liebau G, Kochsiek K (1982) Antidiuretic hormone in congestive heart failure. Am J Med 72(1):49–52CrossRefPubMed Riegger GA, Liebau G, Kochsiek K (1982) Antidiuretic hormone in congestive heart failure. Am J Med 72(1):49–52CrossRefPubMed
19.
go back to reference Schrier RW (2006) Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med 119(7):S47–S53CrossRefPubMed Schrier RW (2006) Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. Am J Med 119(7):S47–S53CrossRefPubMed
20.
go back to reference Schrier RW, Gross P, Gheorghiade M et al (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 355(20):2099–2112CrossRefPubMed Schrier RW, Gross P, Gheorghiade M et al (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 355(20):2099–2112CrossRefPubMed
21.
22.
go back to reference Rossi J, Bayram M, Udelson JE et al (2007) Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial. Acute Card Care 9(2):82–86CrossRefPubMed Rossi J, Bayram M, Udelson JE et al (2007) Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial. Acute Card Care 9(2):82–86CrossRefPubMed
23.
go back to reference 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(12):1319–1331CrossRefPubMed 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(12):1319–1331CrossRefPubMed
24.
go back to reference Gheorghiade M, Gattis WA, O’Connor CM et al (2004) Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291(16):1963–1971CrossRefPubMed Gheorghiade M, Gattis WA, O’Connor CM et al (2004) Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291(16):1963–1971CrossRefPubMed
25.
go back to reference Rajendran R, Grossman A, Kar P (2012) Vasopressin receptor antagonist in the treatment of the syndrome of inappropriate antidiuretic hormone in general hospital practice. Endocr J 59(10):903–909CrossRefPubMed Rajendran R, Grossman A, Kar P (2012) Vasopressin receptor antagonist in the treatment of the syndrome of inappropriate antidiuretic hormone in general hospital practice. Endocr J 59(10):903–909CrossRefPubMed
26.
go back to reference Torres VE, Chapman AB, Devuyst O et al (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367(25):2407–2418CrossRefPubMedPubMedCentral Torres VE, Chapman AB, Devuyst O et al (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367(25):2407–2418CrossRefPubMedPubMedCentral
27.
go back to reference Verbalis JG, Grossman AB, Höybye C, Runkle I (2014) Review and analysis of differing regulatory indications and expert panel guidelines for the treatment of hyponatremia. Curr Med Res Opin 30(7):1201–1207CrossRefPubMed Verbalis JG, Grossman AB, Höybye C, Runkle I (2014) Review and analysis of differing regulatory indications and expert panel guidelines for the treatment of hyponatremia. Curr Med Res Opin 30(7):1201–1207CrossRefPubMed
28.
go back to reference Verbalis JG, Goldsmith SR, Greenberg G et al (2013) Diagnosis, evaluation and treatment of hyponatremia: expert panel recommendations. Am J Med 126(10):S1–S42CrossRefPubMed Verbalis JG, Goldsmith SR, Greenberg G et al (2013) Diagnosis, evaluation and treatment of hyponatremia: expert panel recommendations. Am J Med 126(10):S1–S42CrossRefPubMed
29.
30.
go back to reference Inomata T, Izumi T, Matsuzaki M, Hori M, Hirayama A, Investigators Tolvaptan (2011) Phase III clinical pharmacology study of tolvaptan. Cardiovasc Drugs Ther 25(1):S57–S65CrossRefPubMed Inomata T, Izumi T, Matsuzaki M, Hori M, Hirayama A, Investigators Tolvaptan (2011) Phase III clinical pharmacology study of tolvaptan. Cardiovasc Drugs Ther 25(1):S57–S65CrossRefPubMed
31.
go back to reference Sakaida I, Yanase M, Kobayashi Y et al (2012) The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study. J Int Med Res 40(6):2381–2393CrossRefPubMed Sakaida I, Yanase M, Kobayashi Y et al (2012) The pharmacokinetics and pharmacodynamics of tolvaptan in patients with liver cirrhosis with insufficient response to conventional diuretics: a multicentre, double-blind, parallel-group, phase III study. J Int Med Res 40(6):2381–2393CrossRefPubMed
32.
go back to reference Kenz S, Haas CS, Werth SC, Bohnet S, Brabant G (2011) High sensitivity to tolvaptan in paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Ann Oncol 22(12):2696CrossRefPubMed Kenz S, Haas CS, Werth SC, Bohnet S, Brabant G (2011) High sensitivity to tolvaptan in paraneoplastic syndrome of inappropriate ADH secretion (SIADH). Ann Oncol 22(12):2696CrossRefPubMed
33.
go back to reference Bartoli E, Castello L, Bergamasco L, Sainaghi PP (2007) A new method to distinguish the hyponatremia of electrolyte loss from that due to pure solvent changes. Eur J Appl Physiol 101(1):133–142CrossRefPubMed Bartoli E, Castello L, Bergamasco L, Sainaghi PP (2007) A new method to distinguish the hyponatremia of electrolyte loss from that due to pure solvent changes. Eur J Appl Physiol 101(1):133–142CrossRefPubMed
34.
go back to reference Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N, Conivaptan Study Group (2007) Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 27(5):447–457 Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N, Conivaptan Study Group (2007) Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 27(5):447–457
35.
go back to reference Gerbes AL, Gulberg V, Ginès P et al (2003) Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology 124(4):933–939CrossRefPubMed Gerbes AL, Gulberg V, Ginès P et al (2003) Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology 124(4):933–939CrossRefPubMed
36.
go back to reference Abraham WT, Hensen J, Gross P et al (2012) Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia. Kidney Int 82(11):1223–1230CrossRefPubMed Abraham WT, Hensen J, Gross P et al (2012) Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia. Kidney Int 82(11):1223–1230CrossRefPubMed
37.
go back to reference Aronson D, Verbalis JG, Mueller M, Krum H, Investigators DILIPO (2011) Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study. Eur J Heart Fail 13(3):327–336CrossRefPubMed Aronson D, Verbalis JG, Mueller M, Krum H, Investigators DILIPO (2011) Short- and long-term treatment of dilutional hyponatraemia with satavaptan, a selective arginine vasopressin V2-receptor antagonist: the DILIPO study. Eur J Heart Fail 13(3):327–336CrossRefPubMed
38.
go back to reference Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U (2010) Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis 56(2):325–337CrossRefPubMed Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U (2010) Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis 56(2):325–337CrossRefPubMed
39.
go back to reference Jaber BL, Almarzouqi L, Borgi L, Seabra VF, Balk EM, Madias NE (2011) Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. Am J Med 124(10):977.e1–9 Jaber BL, Almarzouqi L, Borgi L, Seabra VF, Balk EM, Madias NE (2011) Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. Am J Med 124(10):977.e1–9
40.
go back to reference Tzoulis P, Waung JA, Bagkeris E et al (2015) Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion. Clin Endocrinol. doi:10.1111/cen.12943 Tzoulis P, Waung JA, Bagkeris E et al (2015) Real-life experience of tolvaptan use in the treatment of severe hyponatraemia due to syndrome of inappropriate antidiuretic hormone secretion. Clin Endocrinol. doi:10.​1111/​cen.​12943
41.
go back to reference Verbalis JG, Martinez AJ (1991) Determinants of brain myelinolysis following correction of chronic hyponatremia in rats. In: Jard S, Jamison RL (ed) Vasopressin, Vol 208. Colloque INSERM/John Libbey Eurotext Ltd, Paris, France, pp 539–547 Verbalis JG, Martinez AJ (1991) Determinants of brain myelinolysis following correction of chronic hyponatremia in rats. In: Jard S, Jamison RL (ed) Vasopressin, Vol 208. Colloque INSERM/John Libbey Eurotext Ltd, Paris, France, pp 539–547
Metadata
Title
Efficacy and safety of two different tolvaptan doses in the treatment of hyponatremia in the Emergency Department
Authors
Luigi Mario Castello
Marco Baldrighi
Alice Panizza
Ettore Bartoli
Gian Carlo Avanzi
Publication date
01-10-2017
Publisher
Springer International Publishing
Published in
Internal and Emergency Medicine / Issue 7/2017
Print ISSN: 1828-0447
Electronic ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-016-1508-5

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