Hyponatremia in critically ill patients is a common and challenging problem. Increased levels of arginine vasopressin almost always contribute to the etiology. Inhibition of the vasopressin receptor with a vasopressin receptor antagonist (vaptan) is a novel approach to the treatment of hyponatremia. Vaptans are well suited to the treatment of chronic hyponatremia associated with syndrome of inappropriate anti-diuretic hormone secretion (SIADH) and hypervolemic states like cirrhosis or congestive heart failure. No data are available on the use of vaptans in acute hyponatremia, and they are not indicated in hypovolemic hyponatremia. The focus of this review is the treatment of critically ill patients with hyponatremia with vaptans and other measures.
UpadhyayAJaberBLMadiasNE. Incidence and prevalence of hyponatremia. Am J Med. 2006;119(7 suppl 1):S30–S35.
2.
AdrogueHJMadiasNE. Hyponatremia. N Engl J Med. 2000;342(20):1581–1589.
3.
SchrierRW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2). N Engl J Med. 1988;319(17):1127–1134.
4.
SchrierRW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (1). N Engl J Med. 1988;319(16):1065–1072.
5.
DeVitaMVGardenswartzMHKoneckyAZabetakisPM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163–166.
6.
AndersonRJChungHMKlugeRSchrierRW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1958;102(2):164–168.
LehrichRWGreenbergA. When is it appropriate to use vasopressin receptor antagonists?J Am Soc Nephrol. 2008;19(6):1054–1058.
9.
FraserCLArieffAI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997;102(1):67–77.
10.
SedlacekMSchoolwerthACRemillardBD. Electrolyte disturbances in the intensive care unit. Semin Dial. 2006;19(6):496–501.
11.
BennaniSLAbouqalRZeggwaghAA. [Incidence, causes and prognostic factors of hyponatremia in intensive care]. Rev Med Interne. 2003;24(4):224–229.
12.
FriedmanEShadelMHalkinHFarfelZ. Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann Intern Med. 1989;110(1):24–30.
13.
SonnenblickMAlgurNRosinA. Thiazide-induced hyponatremia and vasopressin release.[comment]. Ann Int Med. 1989;110(9):751.
14.
SonnenblickMFriedlanderYRosinAJ. Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. [Review] [66 refs]. Chest. 1993;103(2):601–606.
15.
FriedmanEShadelMHalkinHFarfelZ. Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis [see comment]. Ann Int Med. 1989;110(1):24–30.
16.
HarriganMR. Cerebral salt wasting syndrome. Crit Care Clin. 2001;17:125–138.
17.
BerendesEWalterMCullenP. Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet. 1997;349:245–249.
18.
MaesakaJKImbrianoLJAliNMIlamathiE. Is it cerebral or renal salt wasting?Kidney Int. 2009;76(9):934–938.
19.
SternsRHSilverSM. Cerebral salt wasting versus SIADH: what difference?J Am Soc Nephrol. 2008;19(2):194–196.
20.
SchwartzWBBennettWCurelopSBartterFC. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med. 1957;23(4):529–542.
21.
BartterFCSchwartzWB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967;42:790–806.
22.
KleinLO’ConnorCMGattisWA. Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations. Am J Cardiol. 2003;91(9A):18F–40F.
23.
MartinPYGinesPSchrierRW. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med. 1998;339(8):533–541.
24.
GinesPSchrierRW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279–1290.
25.
ArieffAILlachFMassrySG. Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine. 1976;55(2):121–129.
26.
VerbalisJGGullansSR. Hyponatremia causes large sustained reductions in brain content of multiple organic osmolytes in rats. Brain Res. 1991;567(2):274–282.
27.
GullansSRVerbalisJG. Control of brain volume during hyperosmolar and hypoosmolar conditions. Annu Rev Med. 1993;44:289–301.
28.
SonnenblickMFriedlanderYRosinAJ. Diuretic-induced severe hyponatremia. Review and analysis of 129 reported patients. Chest. 1993;103(2):601–606.
29.
LauriatSMBerlT. The hyponatremic patient: practical focus on therapy. J Am Soc Nephrol. 1997;8:1599–1607.
30.
NorenbergMDLeslieKORobertsonAS. Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol. 1982;11(2):128–135.
31.
WrightDGLaurenoRVictorM. Pontine and extrapontine myelinolysis. Brain. 1979;102(2):361–385.
32.
BurcarPJNorenbergMDYarnellPR. Hyponatremia and central pontine myelinolysis. Neurology. 1977;27(3):223–226.
33.
LaurenoRKarpBI. Myelinolysis after correction of hyponatremia. Ann Intern Med. 1997;126(1):57–62.
34.
VerbalisJGMartinezAJ. Neurological and neuropathological sequelae of correction of chronic hyponatremia. Kidney Int. 1991;39(6):1274–1282.
35.
SternsRHCappuccioJDSilverSM. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4(8):1522–1530.
KnepperMA. Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol. 1997;272(1 pt 2):F3–12.
42.
ThibonnierMConartyDMPrestonJA. Molecular pharmacology of human vasopressin receptors. Adv Exp Med Biol. 1998;449:251–276.
43.
AguileraG. Regulation of pituitary ACTH secretion during chronic stress. Front Neuroendocrinol. 1994;15(4):321–350.
YamamuraYOgawaHYamashitaH. Characterization of a novel aquaretic agent, OPC-31260, as an orally effective, nonpeptide vasopressin V2 receptor antagonist. Br J Pharmacol. 1992;105(4):787–791.
47.
OhnishiAOritaYOkaharaR. Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men. J Clin Invest. 1993;92(6):2653–2659.
48.
ShimizuK. Aquaretic effects of the nonpeptide V2 antagonist OPC-31260 in hydropenic humans. Kidney Int. 1995;48(1):220–226.
49.
SaitoTIshikawaSAbeK. Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Clin Endocrinol Metab. 1997;82(4):1054–1057.
50.
BurnierMFrickerAFHayozDNussbergerJBrunnerHR. Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects. Eur J Clin Pharmacol. 1999;55(9):633–637.
51.
Macion-DazardRCallahanNXuZWuNThibonnierMShohamM. Mapping the binding site of six nonpeptide antagonists to the human V2-renal vasopressin receptor. J Pharmacol Exp Ther. 2006;316(2):564–571.
52.
PerianayagamASternsRHSilverSM. DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clin J Am Soc Nephrol. 2008;3(2):331–336.
53.
MohmandHKIssaDAhmadZCappuccioJDKouidesRWSternsRH. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clin J Am Soc Nephrol. 2007;2(6):1110–1117.
54.
DecauxG. 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(7):582–584.
55.
GhaliJKKorenMJTaylorJR. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006;91(6):2145–2152.
56.
ZeltserDRosanskySvan RensburgHVerbalisJGSmithNConivaptan Study Group Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.Am J Nephrol. 2007;27(5):447–457.
57.
SchrierRWGrossPGheorghiadeM. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099–2112.
58.
LeeCRWatkinsMLPattersonJH. Vasopressin: a new target for the treatment of heart failure. Am Heart J. 2003;146(1):9–18.
59.
SzatalowiczVLArnoldPEChaimovitzCBichetDBerlTSchrierRW. Radioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. N Engl J Med. 1981;305(5):263–266.
60.
NaitohMSuzukiHMurakamiM. Effects of oral AVP receptor antagonists OPC-21268 and OPC-31260 on congestive heart failure in conscious dogs. Am J Physiol. 1994;267(6 pt 2):H2245–2254.
61.
MartinPYAbrahamWTLiemingX. Selective V2-receptor vasopressin antagonism decreases urinary aquaporin-2 excretion in patients with chronic heart failure. J Am Soc Nephrol. 1999;10(10):2165–2170.
62.
GheorghiadeMGattisWAO’ConnorCM. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA. 2004;291(16):1963–1971.
63.
GheorghiadeMNiaziIOuyangJ. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003;107(21):2690–2696.
64.
GheorghiadeMKonstamMABurnettJCJr. 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):1332–1343.
65.
KonstamMAGheorghiadeMBurnettJCJr. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297(12):1319–1331.
66.
BichetDSzatalowiczVChaimovitzC. Role of vasopressin in abnormal water excretion in cirrhotic patients. Ann Intern Med. 1982;96(4):413–417.
67.
NiederbergerMMartinPYGinesP. Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats. Gastroenterology. 1995;109(5):1624–1630.
68.
MartinPYOharaMGinesP. Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. J Clin Invest. 1998;101(1):235–242.
69.
ClariaJJimenezWArroyoV. Blockade of the hydroosmotic effect of vasopressin normalizes water excretion in cirrhotic rats. Gastroenterology. 1989;97(5):1294–1299.
70.
AsahinaYIzumiNEnomotoN. Increased gene expression of water channel in cirrhotic rat kidneys. Hepatology. 1995;21(11):169–173.
71.
FujitaNIshikawaSESasakiS. Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats. Am J Physiol. 1995;269(6 pt 2):F926–931.
72.
InoueTOhnishiAMatsuoA. Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired water handling in cirrhosis. Clin Pharmacol Ther. 1998;63(5):561–570.
73.
GerbesALGulbergVGinesP. Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology. 2003;124(4):933–939.
74.
WongFBleiATBlendisLMThuluvathPJ. A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter, randomized, placebo-controlled trial. Hepatology. 2003;37(1):182–191.
75.
BhardwajA. Neurological impact of vasopressin dysregulation and hyponatremia. Ann Neurol. 2006;59(2):229–236.
76.
HasanDWijdicksEFVermeulenM. Hyponatremia is associated with cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage. Ann Neurol. 1990;27(1):106–108.
77.
KarandanisDShulmanJA. Recent survey of infectious meningitis in adults: review of laboratory findings in bacterial, tuberculous, and aseptic meningitis. South Med J. 1976;69(4):449–457.
78.
WijdicksEFVermeulenMHijdraAvan GijnJ. Hyponatremia and cerebral infarction in patients with ruptured intracranial aneurysms: is fluid restriction harmful?Ann Neurol. 1985;17(2):137–140.
79.
MurphyTDharRDiringerM. Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care. 2009;11(1):14–19.
