Subscribe to RSS
DOI: 10.1055/s-0031-1275827
© Georg Thieme Verlag KG Stuttgart · New York
Therapie der Hyponatriämie: neue Erkenntnisse und Kontroversen
Treatment of hyponatremia: new developments and controversiesPublication History
eingereicht: 20.10.2010
akzeptiert: 27.1.2011
Publication Date:
26 April 2011 (online)

Zusammenfassung
Die Behandlungsoptionen bei euvolämer Hyponatriämie waren lange Zeit begrenzt. Vasopressin- (ADH-) Rezeptor-Antagonisten, auch unter dem Namen Vaptane oder Aquaretika bekannt, sind eine neue Klasse von Medikamenten, welche nun eine zusätzliche kausale medikamentöse Therapieoption für hyponatriäme Patienten mit euvolämer Hyponatremia aufgrund eines SIADH bieten. Das in Europa zugelassene Tolvaptan antagonisiert nur die antiduretische Vasopressin-Wirkung ohne primär den Blutdruck zu beeinflussen. Es kommt dosisabhängig zur vermehrten Ausscheidung von freiem Wasser (Aquarese). Der primäre Einsatz muss in einem Krankenhaus erfolgen und eng überwacht werden. Die Schwere der neurologischen Symptomatik der Hyponatriämie sollte Richtschnur für die Wahl des therapeutischen Vorgehen sein. Bei der häufig vorkommenen euvolämen Hyponatriämie mit mittelschwerer Symptomatik und dem Vorliegen des Syndrom der inappropriaten ADH-Sekretion (SIADH) ist neben der Trinkmengenrestriktion der Einsatz von Tolvaptan zu erwägen. Bei sehr schwerer zerebraler Symptomatik aufgrund eines akuten Hirnödems ist hingegen weiterhin zügiges, aber symptomlimitiertes und eng kontrolliertes Vorgehen unter Einsatz von 3 %-iger Kochsalzlösung erforderlich. Differentialtherapeutisch stellt das neue Therapieprinzip der Aquaretika eine enorme Bereicherung der Behandlung der symptomatischen Hyponatriämie bei SIADH dar. In der überwiegenden Zahl der Fälle kann die kostenintensive Therapie nach Normalisierung von Serum-Natrium wieder beendet werden.
Abstract
This article summarizes improvements in diagnosis and therapy in patients with symptomatic hyponatremia. The available treatment options for hyponatremia have been limited, and consisted mainly of isotonic or hypertonic saline, urea, and fluid restriction. Vasopressin receptor antagonists, also known as vaptans or aquaretics are a new class of drugs that now offer an additional treatment option for hyponatremic patients with euvolemic hyponatremia due to SIADH in Europe. In short and long term studies, tolvaptane has been shown to be effective in raising serum sodium levels in a predictable fashion in patients with SIADH with only few side effects, when serum sodium was frequently monitored and dosage of tolvaptans was properly adjusted. Further studies are needed to find out which patients benefit from treatment with respect to morbidity and mortality. Until now, therapy is limited to the treatment of moderate symptomatic hyponatremia in SIADH due to the high cost of therapy.
Schlüsselwörter
Hyponatriämie - euvoläme Hyponatriämie - SIADH - Vaptane - Aquaretika - Tolvaptan - hyponatriämische Encephalopathie
Keywords
hyponatremia - euvolemic hyponatremia - SIADH - aquaretics - vaptans - Tolvaptan - hypertonic saline
Literatur
- 1
Anderson R J, Chung H M, Kluge R, Schrier R W.
Hyponatremia:
a prospective analysis of its epidemiology and the pathogenetic
role of vasopressin.
Ann Intern Med.
1985;
102
164-168
Reference Ris Wihthout Link
- 2
Bartter F C, Schwartz W B.
The syndrome
of inappropriate secretion of antidiuretic hormone.
Am
J Med.
1967;
42
790-806
Reference Ris Wihthout Link
- 3
Berl T, Quittnat-Pelletier F, Verbalis J G, Schrier R W, Bichet D G, Ouyang J. et
al .
Oral tolvaptan is safe and effective in chronic
hyponatremia.
J Am Soc Nephrol.
2010;
21
705-712
Reference Ris Wihthout Link
- 4
Decaux G.
Long-term treatment of patients with inappropriate secretion of
antidiuretic hormone by the vasopressin receptor antagonist conivaptan,
urea, or furosemide.
Am J Med.
2001;
110
582-584
Reference Ris Wihthout Link
- 5
Diederich S, Franzen N, Bähr V, Oelkers W.
Severe hyponatremia
due to hypopituitarism with adrenal insufficiency: report on 28
cases.
Eur J Endocrinol.
2003;
148
609-617
Reference Ris Wihthout Link
- 6
Ellison D H, Berl T.
Clinical practice. The
syndrome of inappropriate antidiuresis.
N Engl J Med.
2007;
356
2064-2072
Reference Ris Wihthout Link
- 7
Fenske W, Störk S, Koschker A. et al .
Value of fractional uric acid excretion in
differential diagnosis of hyponatremic patients on diuretics.
J Clin Endocrinol Metab.
2008;
93
2991-2997
Reference Ris Wihthout Link
- 8
Gheorghiade M, Konstam M A, Burnett J C. et al .
Short-term clinical effects
of tolvaptan, an oral vasopressin antagonist, in patients hospitalized
for heart failure: the EVEREST Clinical Status Trials.
J
Am Med Assoc.
2007;
297
1332-1343
Reference Ris Wihthout Link
- 9
Greenberg A, Lehrich R W.
Treatment
of chronic hyponatremia: now we know how, but do we know when or
if?.
J Am Soc Nephrol.
2010;
21
552-555
Reference Ris Wihthout Link
- 10
Gross P, Palm C.
Thiazides: do they kill?.
Nephrol Dial Transplant.
2005;
20
2299-2301
Reference Ris Wihthout Link
- 11
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
870-875
Reference Ris Wihthout Link
- 12
Hensen J, Henig A, Fahlbusch R, Meyer M, Boehnert M, Buchfelder M.
Prevalence, predictors
and patterns of postoperative polyuria and hyponatraemia in the
immediate course after transsphenoidal surgery for pituitary adenomas.
Clin Endocrinol.
1999;
50
431-439
Reference Ris Wihthout Link
- 13
Hoorn E J, Halperin M L, Zietse R.
Diagnostic approach to a patient with hyponatraemia: traditional
versus physiology-based options.
Quart J Med.
2005;
98
529-540
Reference Ris Wihthout Link
- 14
Huda M SB, Boyd A, Skagen K. et
al .
Investigation and management of severe hyponatraemia
in a hospital setting.
Postgrad Med J.
2006;
82
216-219
Reference Ris Wihthout Link
- 15
Konstam M A, Gheorghiade M, Burnett J C. et al .
Effects of oral tolvaptan
in patients hospitalized for worsening heart failure: the EVEREST
Outcome Trial.
J Am Med Assoc.
2007;
297
1319-1331
Reference Ris Wihthout Link
- 16
Okita K, Sakaida I, Okada M. et
al .
A multicenter, open-label, dose-ranging study to
exploratively evaluate the efficacy, safety, and dose-response of tolvaptan
in patients with decompensated liver cirrhosis.
J Gastroenterol.
2010;
45
979-987
Reference Ris Wihthout Link
- 17
Renneboog B, Musch W, Vandemergel X, Manto M U, Decaux G.
Mild chronic hyponatremia is associated with falls, unsteadiness,
and attention deficits.
Am J Med.
2006;
119
71.e1-8
Reference Ris Wihthout Link
- 18
Sandhu H S, Gilles E, DeVita M V, Panagopoulos G, Michelis M F.
Hyponatremia is associated with large-bone
fracture in elderly patients.
Int Urol Nephrol.
2009;
41
733-737
Reference Ris Wihthout Link
- 19
Schneider H J, Aimaretti G, Kreitschmann-Andermahr I, Stalla G, Ghigo E.
Hypopituitarism.
Lancet.
2007;
369
1461-1470
Reference Ris Wihthout Link
- 20
Schrier R W, Gross P, Gheorghiade M. et al .
Tolvaptan, a selective oral vasopressin
V2-receptor antagonist, for hyponatremia.
N Engl J Med.
2006;
355
2099-2112
Reference Ris Wihthout Link
- 21
Sterns R H, Cappuccio J D, Silver S M, Cohen E P.
Neurologic
sequelae after treatment of severe hyponatremia: a multicenter perspective.
J Am Soc Nephrol.
1994;
4
1522-1530
Reference Ris Wihthout Link
- 22
Velez J CQ, Dopson S J, Sanders D S, Delay T A, Arthur J M.
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
1524-1531
Reference Ris Wihthout Link
- 23 Verbalis J, Hoorn E J. 12th European
Congress of Endocrinology, Prague, Czech Republic. 2010.
Reference Ris Wihthout Link
- 24
Verbalis J G, Barsony J, Sugimura Y. et al .
Hyponatremia-induced osteoporosis.
J
Bone Miner Res.
2010;
25
554-563
Reference Ris Wihthout Link
- 25
Verbalis J G, Goldsmith S R, Greenberg A, Schrier R W, Sterns R H.
Hyponatremia treatment guidelines
2007: expert panel recommendations.
Am J Med.
2007;
120
(Suppl 1)
S1-21
Reference Ris Wihthout Link
- 26
Verbalis J G, Gullans S R.
Hyponatremia
causes large sustained reductions in brain content of multiple organic
osmolytes in rats.
Brain Res.
1991;
567
274-282
Reference Ris Wihthout Link
- 27
Waikar S S, Mount D B, Curhan G C.
Mortality after hospitalization with mild,
moderate, and severe hyponatremia.
Am J Med.
2009;
122
857-865
Reference Ris Wihthout Link
Prof. Dr. med. Johannes Hensen
Medizinische Klinik
Klinikum Nordstadt
Klinikum
Region Hannover
Haltenhoffstr. 41
30167 Hannover
Email: johannes.hensen@krh.eu