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Open Access 01-12-2016 | Research

Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients

Authors: Michele Umbrello, Elena S. Mantovani, Paolo Formenti, Claudia Casiraghi, Davide Ottolina, Martina Taverna, Angelo Pezzi, Giovanni Mistraletti, Gaetano Iapichino

Published in: Annals of Intensive Care | Issue 1/2016

Abstract

Background

Hyponatremia is the most common electrolyte disturbance in hospitalized patients, and it represents a well-established risk factor for ICU/hospital mortality. The majority of hyponatremic states are associated with elevated arginine vasopressin levels and a preserved sodium pool. Conventional treatment is either not pathophysiologically oriented or of limited effectiveness. The aim of the present study is to investigate the use of enteral Tolvaptan in critically ill hyponatremic patients.

Methods

This is a retrospective observational study in a general ICU. Patients with preserved sodium pool hyponatremia refractory to conventional therapy were enrolled. The hemodynamic, renal, and hepatic functions, together with sodium and water balance as close as possible to the drug administration and up to 72 h thereafter, were analyzed. The main outcome was a serum sodium increase of ≥ 4 mmol/L in 24 h; secondary endpoints were the ability to maintain serum sodium at 24 and 72 h, a decrease in urine sodium concentration and an increase in sodium-free diuresis.

Results

38 patients were enrolled. The average dose of enteral Tolvaptan was 7.5 mg. 31 patients (81.6 %) increased their serum sodium >4 mmol/l/24 h; the average increase was 6.7 ± 3.4 mmol/l during the first 24 h (p < 0.001 vs baseline), and this was sustained at 72 h. No adverse effects were reported. Plasma sodium (R = −0.622, p < 0.001), urine sodium (R = −0.345, p < 0.001), central venous oxygen saturation (R = 0.401, p = 0.013), and BUN (R = −0.416, p = 0.031) before Tolvaptan were all significantly correlated with the absolute increase in serum sodium after the administration.

Conclusions

Enteral administration of Tolvaptan seems effective in the treatment of hyponatremia with preserved sodium pool in critically ill patients. Even if the study was underpowered to detect significant side effects or complications of unwarranted fast corrections of hyponatremia, we report no complications.

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Waikar SS, Mount DB, Curhan GC. Mortality after hospitalization with mild, moderate, and severe hyponatremia. Am J Med. 2009;122(9):857–65. doi:10.1016/j.amjmed.2009.01.027.PubMedCentralCrossRefPubMed

Bennani SL, Abouqal R, Zeggwagh AA, Madani N, Abidi K, Zekraoui A, et al. Incidence, causes and prognostic factors of hyponatremia in intensive care. Rev Med Interne. 2003;24(4):224–9.CrossRefPubMed

Funk GC, Lindner G, Druml W, Metnitz B, Schwarz C, Bauer P, et al. Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med. 2010;36(2):304–11. doi:10.1007/s00134-009-1692-0.CrossRefPubMed

Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, Laupland K. The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units. Crit Care. 2008;12(6):R162. doi:10.1186/cc7162.PubMedCentralCrossRefPubMed

Greenberg A, Verbalis JG, Amin AN, Burst VR, Chiodo JA 3rd, Chiong JR, et al. Current treatment practice and outcomes. Report of the hyponatremia registry. Kidney Int. 2015;88(1):167–77. doi:10.1038/ki.2015.4.PubMedCentralCrossRefPubMed

Sterns RH. Disorders of plasma sodium–causes, consequences, and correction. N Engl J Med. 2015;372(1):55–65. doi:10.1056/NEJMra1404489.CrossRefPubMed

Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med. 2006;119(7 Suppl 1):S36–42. doi:10.1016/j.amjmed.2006.05.006.CrossRefPubMed

Adler SM, Verbalis JG. Disorders of body water homeostasis in critical illness. Endocrinol Metab Clin North Am. 2006;35(4):873–94. doi:10.1016/j.ecl.2006.09.011.CrossRefPubMed

Schrier RW, Berl T. Nonosmolar factors affecting renal water excretion (first of two parts). N Engl J Med. 1975;292(2):81–8. doi:10.1056/NEJM197501092920207.CrossRefPubMed

10.

Palm C, Pistrosch F, Herbrig K, Gross P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006;119(7 Suppl 1):S87–92. doi:10.1016/j.amjmed.2006.05.014.CrossRefPubMed

11.

Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1–42. doi:10.1016/j.amjmed.2013.07.006.CrossRefPubMed

12.

Decaux G, Unger J, Brimioulle S, Mockel J. Hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Rapid correction with urea, sodium chloride, and water restriction therapy. JAMA. 1982;247(4):471–4.CrossRefPubMed

13.

Hantman D, Rossier B, Zohlman R, Schrier R. Rapid correction of hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. An alternative treatment to hypertonic saline. Ann Intern Med. 1973;78(6):870–5.CrossRefPubMed

14.

Cherrill DA, Stote RM, Birge JR, Singer I. Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion. Ann Intern Med. 1975;83(5):654–6.CrossRefPubMed

15.

Decaux G, Unger J, Mockel J. Urea therapy for inappropriate antidiuretic hormone secretion from tuberculous meningitis. JAMA. 1980;244(6):589–90.CrossRefPubMed

16.

Soupart A, Decaux G. Therapeutic recommendations for management of severe hyponatremia: current concepts on pathogenesis and prevention of neurologic complications. Clin Nephrol. 1996;46(3):149–69.PubMed

17.

Jaber BL, Almarzouqi L, Borgi L, Seabra SF, Balk EM, Madias NE. Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. Am J Med. 2011;124(10):977. doi:10.1016/j.amjmed.2011.04.028 (e1–9).PubMedCentralCrossRefPubMed

18.

Decaux G, Waterlot Y, Genette F, Hallemans R, Demanet JC. Inappropriate secretion of antidiuretic hormone treated with frusemide. Br Med J (Clin Res Ed). 1982;285(6335):89–90.CrossRef

19.

Greenberg A. Diuretic complications. Am J Med Sci. 2000;319(1):10–24.CrossRefPubMed

20.

Zietse R, van der Lubbe N, Hoorn EJ. Current and future treatment options in SIADH. NDT plus. 2009;2(Suppl_3):iii12–9. doi:10.1093/ndtplus/sfp154.PubMedCentralPubMed

21.

Decaux G, Andres C, Gankam Kengne F, Soupart A. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care. 2010;14(5):R184. doi:10.1186/cc9292.PubMedCentralCrossRefPubMed

22.

Berl T. Vasopressin antagonists. N Engl J Med. 2015;372(23):2207–16. doi:10.1056/NEJMra1403672.CrossRefPubMed

23.

Imamura T, Kinugawa K, Minatsuki S, Muraoka H, Kato N, Inaba T, et al. Urine sodium excretion after tolvaptan administration is dependent upon baseline serum sodium levels: a possible explanation for the improvement of hyponatremia with scarce chance of hypernatremia by a vasopressin receptor antagonist. Int Heart J. 2014;55(2):131–7.CrossRefPubMed

24.

Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099–112. doi:10.1056/NEJMoa065181.CrossRefPubMed

25.

Cyr PL, Slawsky KA, Olchanski N, Krasa HB, Goss TF, Zimmer C, et al. Effect of serum sodium concentration and tolvaptan treatment on length of hospitalization in patients with heart failure. Am J Health Syst Pharm. 2011;68(4):328–33. doi:10.2146/ajhp100217.CrossRefPubMed

26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297(12):1332–43. doi:10.1001/jama.297.12.1332.CrossRefPubMed

27.

Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U. Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis. 2010;56(2):325–37. doi:10.1053/j.ajkd.2010.01.013.CrossRefPubMed

28.

Verrua E, Mantovani G, Ferrante E, Noto A, Sala E, Malchiodi E, et al. Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature. Hormones (Athens). 2013;12(1):135–41.

29.

Mantovani E, Pirrone M, Spanu P, Albicini M, Gandola A, Ottolina D, et al. Hypo-osmolar fluid absorption in endoscopic resection: a new pharmacological approach. Minerva Anestesiol. 2015;81(5):591–2.PubMed

30.

Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967;42(5):790–806.CrossRefPubMed

31.

Verbalis JG, Zeltser D, Smith N, Barve A, Andoh M. Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study. Clin Endocrinol. 2008;69(1):159–68. doi:10.1111/j.1365-2265.2007.03149.x.CrossRef

32.

Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007;27(5):447–57. doi:10.1159/000106456.CrossRefPubMed

33.

Velez JC, Dopson SJ, Sanders DS, Delay TA, Arthur JM. Intravenous conivaptan for the treatment of hyponatraemia caused by the syndrome of inappropriate secretion of antidiuretic hormone in hospitalized patients: a single-centre experience. Nephrol Dial Transplant. 2010;25(5):1524–31. doi:10.1093/ndt/gfp731.CrossRefPubMed

34.

Nguyen MK, Kurtz I. Derivation of a new formula for calculating urinary electrolyte-free water clearance based on the Edelman equation. Am J Physiol Renal Physiol. 2005;288(1):F1–7. doi:10.1152/ajprenal.00259.2004.CrossRefPubMed

35.

Hall JE. Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia: Saunders; 2011.

36.

Haussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet. 1993;341(8856):1330–2.CrossRefPubMed

37.

Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294–302. doi:10.1001/archinternmed.2009.513.CrossRefPubMed

38.

Friedman B, Cirulli J. Hyponatremia in critical care patients: frequency, outcome, characteristics, and treatment with the vasopressin V2-receptor antagonist tolvaptan. J Crit Care. 2013;28(2):219. doi:10.1016/j.jcrc.2012.06.001 (e1–12).CrossRefPubMed

39.

Dasta JF, Chiong JR, Christian R, Lin J. Evaluation of costs associated with tolvaptan-mediated hospital length of stay reduction among US patients with the syndrome of inappropriate antidiuretic hormone secretion, based on SALT-1 and SALT-2 trials. Hosp Pract (1995). 2012;40(1):7–14. doi:10.3810/hp.2012.02.942.CrossRef

40.

Naidech AM, Paparello J, Liebling SM, Bassin SL, Levasseur K, Alberts MJ, et al. Use of Conivaptan (Vaprisol) for hyponatremic neuro-ICU patients. Neurocrit Care. 2010;13(1):57–61. doi:10.1007/s12028-010-9379-5.CrossRefPubMed

41.

Galton C, Deem S, Yanez ND, Souter M, Chesnut R, Dagal A, et al. Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury. Neurocrit Care. 2011;14(3):354–60. doi:10.1007/s12028-011-9525-8.CrossRefPubMed

42.

Iapichino G. Low hemoglobin level with low oncotic pressure in critically ill patients. Is it a safe strategy?. Minerva Anestesiol. 2015.

43.

Iapichino G, Pesenti A, Radrizzani D, Solca M, Pelizzola A, Gattinoni L. Nutritional support to long-term anesthetized and curarized patients under extracorporeal respiratory assist for terminal pulmonary failure. JPEN J Parenter Enteral Nutr. 1983;7(1):50–4.CrossRefPubMed

44.

Mistraletti G, Sabbatini G, Taverna M, Figini MA, Umbrello M, Magni P, et al. Pharmacokinetics of orally administered melatonin in critically ill patients. J Pineal Res. 2010;48(2):142–7. doi:10.1111/j.1600-079X.2009.00737.x.CrossRefPubMed

45.

Metzger BL, DeVita MV, Michelis MF. Observations regarding the use of the aquaretic agent conivaptan for treatment of hyponatremia. Int Urol Nephrol. 2008;40(3):725–30. doi:10.1007/s11255-008-9353-8.CrossRefPubMed

46.

Decaux G, Genette F, Mockel J. Hypouremia in the syndrome of inappropriate secretion of antidiuretic hormone. Ann Intern Med. 1980;93(5):716–7.CrossRefPubMed

47.

Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis. Am J physiol. 1994;267(6 Pt 2):R1617–25.PubMed

Title: Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients
Authors: Michele Umbrello
Elena S. Mantovani
Paolo Formenti
Claudia Casiraghi
Davide Ottolina
Martina Taverna
Angelo Pezzi
Giovanni Mistraletti
Gaetano Iapichino
Publication date: 01-12-2016
Publisher: Springer Paris
Published in: Annals of Intensive Care / Issue 1/2016
Electronic ISSN: 2110-5820
DOI: https://doi.org/10.1186/s13613-015-0096-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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